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Increasing Laboratory Capacity for TB Diagnosis With Aureliana Chambal
2024/03/09
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ASM's Young Ambassador, Aureliana Chambal, discusses the high incidence of tuberculosis in Mozambique and how improved surveillance can help block disease transmission in low resource settings.
Ashley's Biggest Takeaways: Mozambique is severely impacted by the TB epidemic, with one of the highest incidences in Africa (368 cases/ 100,000 people in the population). Human-adapted members of the Mycobacterium tuberculosis complex (MTBC) belong to 7 different phylogenetic lineages . These 7 lineages may vary in geographic distribution, and have varying impacts on infection and disease outcome. For decades, 2 reference strains have been used for TB lab research, H37Rv, which Chambal mentions, and Erdman. Both of these belong to TB Lineage 4. According to Chambal, the reference strains that we use for whole genome sequencing (worldwide) may be missing genes that are related the virulence (and/or resistance) of strains that are circulating in a given population and detected in clinical settings. Chambal is endeavoring to employ a new strain to control these analyses and better understand transmission dynamics in the community setting. Featured Quotes:
The Schlumberger Foundation Faculty for the Future Fellowship is one of my proudest accomplishments for the 2023. I applied for this fellowship last year to pursue my Ph.D. It is a program that supports women coming from emerging and developing economies to pursue advanced research qualifications in science, technology, engineering and mathematics. I applied because I was looking to get more skills in microbiology, specifically tuberculosis, to pursue my Ph.D. at Nottingham Trent University.
Pathway to Microbiology Research
My trajectory is different because I have a bachelor’s in veterinary medicine. And during my undergrad, I always had more interest in the lab practice modules or disciplines. For the end of the [bachelor’s] project, I was looking to understand the anthelmintic effectiveness against the gastrointestinal parasites in goats. After I finished this project, I was looking to continue a related project, but unfortunately, I couldn't get work related to that..
In 2016, I applied for the National Institutes of Health of Mozambique, which is one of the biggest research institutions in my home country. That's when I was selected to work at the north region of Mozambique, specifically at the Nampula Tuberculosis Reference Laboratory. And then I moved to the public health laboratory as well, where I had the opportunity to work in the microbiology section. So, to be honest, my passion for microbiology started when I had the first contact with the TB lab, and then I couldn't separate myself from this area, tuberculosis.
In 2016, I had the opportunity to receive a mentorship. Our lab, the TB lab of Nampula, received mentorship from the American Society for Microbiology. And we worked with Dr. Shirematee Baboolal; she was the mentor of our lab. The main idea of the program was to get the lab accredited and to build technical capacity in the lab. And to be honest, at the time, I didn't have much experience in lab techniques to detect or diagnosis tuberculosis.
And I said to Dr. Shirematee, “I don't have much experience in this area, so, I don't know if I will be able to help you to accomplish these goals.” And she said, “If you want to learn, I can teach you, and you can be one of the best in this area.”
And then we started training with her. It was very interesting. The passion she passed to us about microbiology—and tuberculosis, in particular—was one of the triggers for my passion in this area. So, to be honest, Dr. Shirematee Baboolal was one of the persons that triggered my interest from tuberculosis. So, I have to say thank you to her!
Tuberculosis Genomic Diversity and Transmission Dynamics
Mozambique is one of the higher burden countries of tuberculosis. So, our population is about 33 million people. And the case rate is high, it is approximately 360 per 100,000 people in the population, which is equivalent to over 110,000, which is equivalent 211,000 cases in the population. So, while I was working for the TB lab, I always had the desire to understand more about the transmission of the disease in the community.
And I felt like I didn't have enough skills to do that; I didn't the tools to do that. And I said, “Okay, let me try to look to improve the skills.” That's why for my master's degree I tried to understand the genomic diversity of M. tuberculosis and see how we can see the gene content diversity within the lineage for which is the most spread lineage worldwide, and is predominant in Mozambique. Afterwards, I tried to expand to the other lineages.
When I finished my master's degree, I felt that it was still missing something. I had the information about [TB] diversity, but I didn't get the point about transmission itself. That's why, when I went back and applied for my Ph.D., I structured my current project to specifically look at transmission and transmission clusters in the community.
I'm trying to see how we can expand the gold standard of whole genome sequencing to try to make it applicable for all settings, including the low resources settings where most TB cases happen.
So, M. tuberculosis itself doesn't have a lot of diversity between strains and within strains, because [strains] are very monomorphic. But you can find some genes that are different, specifically from the reference strain that we use, which is H37Rv. In the reference strain for M. tuberculosis , we saw is that many genes are missing—genes that are related to virulence. So, this information can be tricky, because it's the reference that we use worldwide to analyze our samples that come from whole genome sequencing. If we have genes missing, we are not [seeing] the complete information about the virulence of the bacterial strain that is circulating. So, my analysis was trying to understand how we can employ a new strain (that has at least most of the genes that are present in the other screens of the lineage) to control our analysis.
Whole genome sequencing requires a lot of computational resources. So, the main idea is to try to extend that pipeline to make applicable to use in all settings.
In Mozambique, we have whole genome sequencing equipment at the central level of the country, and the demand is high. But there is a queue for processing the samples. So, if we have a pipeline that [makes it so] anyone is able to analyze the data, we can have the results quick, and we can have more information for the public health sector.
And with transmission studies, you can have a clearer idea of where the recent infection happened. We can see how many cases we have and when the transmission started. And then we can [try to] track and block the transmission.
Involvement with ASM Young Ambassador Program
So, I had the opportunity to hear about ASM’s Young Ambassador Program while I was working at the TB lab, in 2018. I spoke to Dr. Shirematee Baboolal and Dr. Maritza Urrego. And they told me about this position. Then, once I finished my masters [program], I applied for that position. I saw the requirements, and I felt like it was the right position for what I wanted to do for my community—to support the youth community and engage with my community back in Mozambique. I applied in 2020, and I got the position.
And I have to say, it is one of the best things I have done so far. Because since the implementation of this program in Mozambique, I have interacted with students in schools and universities. We have developed a lot of workshops. I feel like I can contribute scientifically to improve their lives, to improve their academic lives. And recently, we launched a program called Microbiology Kids Club . We go to schools, in church, and we teach children about science, specifically microbiology. We use cartoons and paint microbes to explain the importance of the microbes for the community for our daily activities. And it's very interesting how they are engaged. I can feel that it's a way to develop the taste for science in the children. So, I'm very happy with this accomplishment. In this role of young ambassador, I feel like I can contribute to my community back home.
I have so many ideas, so many dreams. I don't even know where to start! Because I have the ambitions to support my country back home. After I finish my Ph.D., I would like to create a robust technique that will help us to properly understand the [TB] transmission studies. So hopefully, with my Ph.D., I will be able to do that, or at least contribute something to support not only my country, but all low resources settings.
And I would also like to be like to support some public health policies that can help us. Because we don't have like a strong component that involves the lab, the public health sector—I feel like everything is separated. We need to combine everything if we want to fight against tuberculosis. So, my desire is also to create a link between all these specific sites so we can make our fight against TB stronger. I want to continue [to drive] awareness about the support we need in low resource settings to control the fight against tuberculosis.
Links for the Episode: ASM Ambassador Program. ASM Global Public Health Program.
Good Science, Bad Science and How to Make it Better with Ferric Fang and Arturo Casadevall
2024/01/26
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The scientific process has the power to deliver a better world and may be the most monumental human achievement. But when it is unethically performed or miscommunicated, it can cause confusion and division. Drs. Fang and Casadevall discuss what is good science, what is bad science and how to make it better.
Get the book! Thinking about Science: Good Science, Bad Science, and How to Make It Better
Using AI to Understand How the Gut-Brain Axis Points to Autism With James Morton
2023/12/11
Dr. James Morton discusses how the gut microbiome modulates brain development and function with specific emphasis on how the gut-brain axis points to functional architecture of autism.
Watch James' talk from ASM Microbe 2023: Using AI to Glean Insights From Microbiome Data https://youtu.be/hUQls359Spo
Atypical Metabolism of Leishmania and Other Parasitic and Free-Living Protists With Michael Ginger
2023/10/31
Dr. Michael ginger, Dean of the School of Applied Sciences in the Department of Biological and geographical Science at the University of Huddersfield, in West Yorkshire, England discusses the atypical metabolism and evolutionary cell biology of parasitic and free-living protists, including Leishmania, Naegleria and even euglinids.
IBS Biomarkers and Diagnostic Diapers With Maria Eugenia Inda-Webb
2023/09/22
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Dr. Maria Eugenia Inda-Webb , Pew Postdoctoral Fellow working in the Synthetic Biology Center at MIT builds biosensors to diagnose and treat inflammatory disorders in the gut, like inflammatory bowel disease and celiac disease. She discusses how “wearables,” like diagnostic diapers and nursing pads could help monitor microbiome development to treat the diseases of tomorrow.
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Ashley's Biggest Takeaways Biosensors devices that engineer living organisms or biomolocules to detect and report the presence of certain biomarkers. The device consists of a bioreceptor (bacteria) and a reporter (fluorescent protein or light). Inda-Webb’s lab recently published a paper in Nature about using biosensors (Sub-1.4 cm3 capsule) to detect inflammatory biomarkers in the gut. The work is focused on diagnosing and treating inflammatory bowel disease, but Inda-Webb acknowledged that that is a large research umbrella. The next step for this research is to monitor the use of the biosensor in humans to determine what chemical concentrations are biologically relevant and to show that it is safe for humans to ingest the device. It is believed that the gut microbiome in humans develops in the first 1000 days to 3 years of life. Early dysbiosis in the gut has been linked to disease in adulthood. However, we do not have a good way to monitor (and/or influence) microbiome development. Inda-Webb hopes to use biosensors in diapers (wearables) to monitor microbiome development and prevent common diseases in adulthood. In 2015, Inda-Webb became ASM’s first Agar Art Contest winner for her piece, “Harvest System.” Inda-Webb is the 2023 winner of the ASM Award for Early Career Environmental Research , which recognizes an early career investigator with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings. Learn More About ASM’s Awards Program Featured Quotes:
We engineer bacteria to sense particular molecules of interest—what we call biomarkers—if they are associated with a disease. And then, we engineer a way that the bacteria will produce some kind of molecule that we can measure—what we call reporter—so that could be a fluorescent protein or light, like the one that we have in this device.
The issue is that inflammation in the gut is really very difficult to track. There are no real current technologies to do that. That is like a black box. And so, most of what we measure is what comes out from the gut, and has its limitations. It doesn't really represent the chemical environment that you have inside, especially in areas where you're inflamed. So, we really needed technologies to be able to open a window in these areas.
The final device that I am actually bringing here is a little pill that the patient would swallow and get into the gut. And then they engineer bacteria that the biosensors, will detect, let's say, nitrous oxide, which is a very transient molecule. And the bacteria are engineered to respond to that in some way—to communicate with the electronics that will wirelessly transmit to your cell phone. And from there, to the gastroenterologist.
We make the bacteria produce light. If they sense nitrous oxide, they produce light, the electronics read that, and the [information] finally gets into your phone.
Part of the challenge was that we needed to make the electronics very very tiny to be able to fit inside the capsule. And also, the amount of bacteria that we use also is only one microliter. And so, imagine one microliter of bacteria producing a tiny amount of light. Finally, the electronics need to be able to read it. So that has been also part of the challenge.
In this case, you have 4 different channels. One is a reference, and then the other 3 are the molecule of your choice. So, for example, what we show in the paper here is that we can even follow a metabolic pathway. So, you can see one more molecule turn into the other one, then into the other one. I'm really excited about that. Because normally we kind of guess as things are happening, you know, but here you can see in real time how the different molecules are changing over time. I think that's pretty exciting for microbiologist.
The immediate application would be for a follow up. Let's say the patient is going to have a flare, and so you could predict it more much earlier. Or there's a particular treatment, and you want to see what is happening [inside the gut]. But for me, as a microbiologist, one of the things I'm most excited about will be more in the longer term.
One of my favorite experiments that I do with the students is the Winogradsky column, and everyone gets super excited. So, we all have nice feelings for that. And it’s basically a column where we asked the students to bring mud from a lake, for example, and then some sources of nutrients. And then, after 6months, you will see all the layers, which is super pretty—beautiful, nice colors. But actually, that gives the concept of how the microenvironment helps to define where, or how, bacteria build communities.
And so, what I think this device is going to do is to help us identify what is this microenvironment and to characterize that. And then, from there, to know if [an individual’s] microbiome is leaning towards the disease state, or if it's already in a serious or dangerous situation, to think about treatments that can lead to a more healthy state. So, I would just say it's really to have a window into the gut, and to be able to give personalized treatment for the patient.
So, one application: I was thinking, I'm from the Boston area. So, one problem we have is getting a tick bite, right? After that, you could actually have to go through a very traumatic, antibiotic regime. I would imagine, in that case, you could [use the biosensor to] get the baseline [measurement], and then if you need to take these antibiotics, the doctors can follow how your microbiome is responding to that. Because one of the problems is that antibiotics changed the oxidation level [in the gut], and that really affects a lot the microbiome. To that point, for example, I get to know patients that they were athletes, and then, after antibiotic treatment, they have serious problems with obesity. Their life gets really messed up in many ways.
And so, what I'm thinking is, if we could monitor earlier, there are a lot of ways that we could prevent that. We could give antioxidants; we could change the antibiotic. There are things that I think the doctor could be able to do and still do the treatment that we know.
And of course, [although] we talk a lot about how much trouble antibiotics are, for certain things, we still need [them].
[The multi-diagnostic diaper] is one of my pet projects. I really love it. So yeah, basically, the issue is that the microbiome develops in the first 3 years. People even say like, 1000 days, you know. But there's really no way to monitor that. And now we're seeing that actually, if the microbiome gets affected, there are a lot of diseases that you will see in adult life. So, if we will be able to monitor the microbiome development, I really believe that we'll be able to prevent many of the diseases of tomorrow.
What happens is that babies wear diapers. So, I thought it was really a very good overlap. We call that “wearables,” you know, like devices that you can wear, and then from there, measure something connected with health.
So, in the diaper, I was excited because—different from the challenge with the ingested device, which was so tiny—here, we don't have the limitation of space. So, we could measure maybe 1000 different biomarkers and see how that builds over time.
We can measure so many things. One could be just toxic elements that could be in the environment. I try to do very grounded science, and so, my question is always, ‘what’s the actionable thing to do?’ So, I'm thinking if there was a lot of toxicity, for example, in the carpet, or in the environment where you live, those are the easiest things to change, right?
Then also, other things connecting more with the metabolism. [Often] the parents don't know that the kid has metabolic issues. So, before that starts to build and bring disease, it would be best if you could detect it as early as possible. From there, with symbiotics, we are thinking there are a lot of therapies that could engineer bacteria to produce the enzymes that the kid can’t produce.
We could also [develop] other products, like for example, a t-shirt to measure the sweat. I'm also thinking more of the milk. I'm very excited about how the milk helps to build the microbiome in the right way. And that that's a huge, very exciting area for microbiologists. And so, we could also have nursing pads that also measure [whether] the mother has the right nutrients.
My family, my grandparents were farmers, and in Argentina, really the time for harvest is very important. You can see how the city and really the whole country gets very active. And at that time [during a course Inda-Webb was taking at Cold Spring Harbor] in this course, I could see that with yeast we were having a lot of tools that would allow us to be much more productive in the field. And I thought, ‘Oh, this feels like a harvest system for yeast.’ Yes. So that was how it [Inda-Webb’s winning agar artwork, ‘Harvest System’] came out.
I really love the people. Here, [at ASM Microbe 2023], I really found that how people are bringing so much energy and really wanted to engage and understand and just connect to this idea of human flourishing, right, giving value to something, and saying, ‘okay, we can actually push the limits of what we know.’ How beautiful is that? And you know, we can learn from that. That was very exciting.
ASM Agar Art Contest
Have you ever seen art created in a petri dish using living, growing microorganisms? That's agar art! ASM's annual Agar Art Contest is a chance for you to use science to show off your creative skills.
Submissions Are Now Being Accepted!
This year's contest theme is "Microbiology in Space." Head over to our Contest Details page to get all of the information about what you need to submit your entry. Submissions will be accepted until Oct. 28!
Links for the Episode: Inda-Webb, et al. recent Nature publication: Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ. Bacterial Biosensors: The Future of Analyte Detection.
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
Think Fungus Early: Preventing Angioinvasion Via Early Detection With Gary Procop
2023/09/01
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Dr. Gary Procop, CEO of the American Board of pathology and professor of pathology at the Cleveland Clinic, Lerner School of Medicine discusses the importance of early detection and diagnosis in order to prevent fungal invasion leading to poor outcomes, particularly in immunocompromised patients. He emphasizes the importance of thinking fungus early, shares his passion for mentoring and talks about key updates in the recently released 7th Edition of Larone’s Medically Important Fungi.
Ashley's Biggest Takeaways Many invasive fungal infections are angiotrophic, meaning they actually grow toward, and into, blood vessels. Once the fungus has penetrated the blood vessel, the blood essentially clots, causing tissue downstream from the blood clot to die (infarction). When tissues that have been excised are viewed under the microscope, hyphal elements can be seen streaming toward or invading through the wall of the blood vessels. Once the clot forms, those hyphal elements can be seen in the center of the blood vessel where only blood should be. Antifungals cannot be delivered to areas where the blood supply has stopped. Therefore, treatment requires a combined surgical and medical approach, and the process is very invasive. Early detection can prevent these bad outcomes by allowing antifungal treatment to be administered before angioinvasion occurs. Links for the Episode: Expand your clinical mycology knowledge with the recently released 7th edition of Larone's Medically Important Fungi: A Guide to Identification. Written by a new team of authors, Lars F. Westblade, Eileen M. Burd, Shawn R. Lockhart and Gary W. Procop, this updated edition continues the legacy of excellence established by founding author, Davise H. Larone.
Since its first edition, this seminal text has been treasured by clinicians and medical laboratory scientists worldwide. The 7th edition carries forward the longstanding tradition of providing high-quality content to educate and support the identification of more than 150 of the most encountered fungi in clinical mycology laboratories.
Get your copy today with $1 flat rate shipping within the U.S. or order the e-book! ASM members enjoy 20% off at checkout using the member promo code.
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
Moldy Skin, Invasive Aspergillosis and the Rise of Candida auris With Shawn Lockhart
2023/07/28
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From antifungal resistance to disaster microbiology and tales of visible mold growing across the skin of patients following a tornado in Joplin, Missouri, Dr. Shawn Lockhart, Senior Clinical Laboratory Advisor in the Mycotic Diseases Branch at the CDC talks all things fungi—complete with references to pop TV shows and the recently released 7th Edition of Larone’s Medically Important Fungi.
Links mentioned:
Larone's Medically Important Fungi: A Guide to Identification, 7th Edition (Use code: MCR20 at checkout for 20% off) CDC’s Mycotic Diseases Branch conducts an annual training course on the identification of pathogenic molds.
Microbial Flavor Profiles for Bread and Wine Production With Kate Howell
2023/07/14
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Dr. Kate Howell , Associate Professor of Food Chemistry at the University of Melbourne, Australia discusses how microbes impact the flavor and aroma of food and beverages and shares how microbial interactions can be used to enhance nutritional properties of food and beverage sources.
Ashley's Biggest Takeaways Saccharomyces means sugar-loving fungus. Humans have similar olfactory structures and mechanisms as insects and are similarly attracted to fermenting or rotting fruits produced by Saccharomyces . Research has shown that insects (and humans) prefer yeasts that produce more esters and aromatic compounds. Palm wine is a product that is made from sap collected from palm trees (palm sap) across the tropical band of the world. Fruity flavors appear to be less important to persistence of Saccharomyces strains in an Indonesian palm wine fermentation. This may be because palm wine fermentation is very quick, generally 1-3 days often, with a maximum of 5 days for fermentation to be conducted. Wineries, on the other hand, ferment annually (one fermentation per year/vintage), when the grapes are right. Grape wine fermentations can take 7 days to 2 weeks to complete. So different selections likely take place between the 2 fermentation products. Featured Quotes:
When we start drawing our lens on how microbes produce food for humans, we're coopting a process that happens quite naturally. Here I'll start off talking about Saccharomyces cerevisiae , the main fermenting yeast in food and beverage production, because it's one of the most studied organisms and was the first eukaryote to be sequenced.
Saccharomyces cerevisiae , as the name implies, loves sugar, and it flourishes when there's a lot of sugar in the environment. Where is sugar found? In fruits, and that's done quite deliberately, because fruits develop sugars and flavors and aromas to attract a birds or insects or anything else that can carry their seeds elsewhere for dispersal.
Now, Saccharomyces lies dormant in the environment in a spore before it encounters a sugar-loving environment. And then it replicates very quickly and tends to dominate fermentation. Humans have coopted that into our kitchens, into our meals, into our lives, and we use that process to produce food.
As Saccharomyces starts to use this sugar, it balances up its metabolism. And as it does this, it produces aromas. These aromas have a lot of important characteristics. Humans love them, but insects also love them too.
I've been interested in the yeasts that are found naturally in sourdough starters. Sourdough is a really interesting system. Because you've got yeast and bacteria interacting with one another.
One of the things we are collaborating on with colleagues in France at Inrae, Dr. Delphine Sicard, is to understand some of the non-Saccharomyces yeasts that are naturally occurring in sourdough starters. So here we're looking at a collection of a yeast called Kazachstania humilis and trying to understand how it has adapted to the sourdough environment, how its sustained over time and how different global populations differ to one another.
And this, of course, is of interest to the baking industry because not only do artisanal bakers have sort of an undiscovered wealth of biodiversity in their starters, baking companies also have an interest in using different sorts of flavors and bread for the commercial markets.
The connection between a chemical profile and a person’s sensory preference isn't something that's complete and direct. So, in every method that we use, there's always caveats, but we try to correlate it. Let's start off with the chemical characterization. We use headspace sampling, analytical chemistry, separation with gas chromatography and identification with mass spectrometry.
And we use different 2-dimensional methods to be able to understand what the very small compounds are, and to be able to identify them. We can semi-quantify these to be able to make comparisons between different fermentations.
We know from wine fermentations and understanding preferences of wine that, in some cases, a particular increase, or an abundance of a particular compound, can be extremely attractive. And that might depend on the style of wine.
What we've discovered through this process is that different people prefer different flavors. Makes sense, doesn't it? We like different things. But some really interesting results from our lab, show that people from different cultural backgrounds have different preferences. And here we're using here in Melbourne, I'm very lucky to work with some very talented postdocs and Ph.D. students from China, who have very different preferences for wine than an Australian does. Of course, Australians are quite heterogeneous in their in their cultural diversity as well. But there's certain flavors that our Chinese colleagues tend to prefer. So we decided to investigate this a little bit more.
So for this study, we recruited wine experts from Australia, actively working in the wine industry, and also wine experts from China, working in the wine industry, and brought them to campus and ask them to rate their preferences on particular aromas and flavor characteristics that they noted in a panel of wines. These were very high-quality wines. We knew with wine experts, we couldn't just give them our loved wines, for example, which can be a little bit patchy quality wise. We asked them to rate their preferences, and then we collected saliva samples.
The saliva samples were really interesting. We looked at 2 different aspects. We looked at the proteins that were present in the saliva samples. And we also looked at the oral microbiome. So the salivary microbiome—the bacteria, in particular—that are present. We found some really interesting things. And this has sparked a big area in our lab.
So while the main enzymatic activities in the different groups of participants were quite similar—so esterase activity, Alpha amylase activity were similar—we found that there was a difference in the abundance of proline rich proteins and other potential flavor carrying compounds. Now, this is quite speculative. We'd like to know why this is the case. And so we're delving a little bit further into this area.
What we do know though is that the abundances, especially if these proline rich proteins, is correlated with how people perceive the stringency. Now stringency is one of those characteristics in wine which is quite difficult to appreciate. It’s a lack of drying characteristic on the tongue and in the mouth and oral cavity. Some people find it quite attractive, others don't.
But we found that the abundance of these polyproline-rich proteins correlates with stringency. This is, in fact, found in other studies because proline-rich proteins interact with polyphenols in the wine, and precipitate, which changes the sensation of astringency in the oral cavity. So here we've got a nice link to protein abundance and how people perceive flavor. But we're talking about microbiology, so maybe I should delve into the microbiological aspects of these studies as well.
In that particular study that I'm referring to, we used wines that were naturally fermented, and that's the other variability that we need to consider when we think about wines from different areas. So, a natural fermentation, in a wine sense, is the grapes are harvested, and whatever microflora is present on the grapes will just ferment, and we often don't know what the main fermenting parties are. But if you contrast that with a majority of commercial wine that's produced, mainly in Australia, but also worldwide, it's inoculated with a selected strain of Saccharomyces or maybe 2 selected strains of Saccharomyces , and that tends to produce a fairly similar flavor profile, regardless of region.
So, you can flatten out geographical characteristics and indications of flavor by inoculating a particular strain of yeast to ferment. That's not true with a natural fermentation, because that's conducted by the yeasts, and also the bacteria which just happened to be in the environment. So, I agree with you there is a lot of regional variation with wine flavor. And we can correlate that with regional diversity of yeast, but only if the wines are naturally fermented not if they're inoculated with a selected strain.
Links for the Episode: LC-ESI-QTOF/MS Characterisation of Phenolic Acids and Flavonoids in Polyphenol-Rich Fruits and Vegetables and Their Potential Antioxidant Activities. Frozen, canned or fermented: when you can't shop often for fresh vegetables, what are the best alternatives? Early Prediction of Shiraz Wine Quality Based on Small Volatile Compounds in Grapes. Building the climate resilience of Melbourne's Food System.
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
AncientBiotics With Steve Diggle and Freya Harrison
2023/06/02
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Dr. Steve Diggle, ASM Distinguished Lecturer and Microbiology Professor at the Georgia Institute of Technology in Atlanta, Georgia and Dr. Freya Harrison, Associate Microbiology Professor at the University of Warwick in Coventry, U.K., discuss the science behind medieval medical treatments and the benefits of interdisciplinary research.
Ashley's Biggest Takeaways Diggle and Harrison met in Oxford, where Harrison was finishing up her Ph.D. and Diggle was doing background research for his work studying evolutionary questions about quorum sensing. When Diggle began searching for a postdoc, Harrison, who had been conducting an independent fellowship at Oxford and studying social evolution, applied. The AncientBiotics Consortium is a group of experts from the sciences, arts and humanities, who are digging through medieval medical books in hopes of finding ancient solutions to today’s growing threat of antibiotic resistance. The group’s first undertaking was recreation and investigation of the antimicrobial properties of an ancient eyesalve described in Bald’s Leechbook, one of the earliest known medical textbooks, which contains recipes for medications, salves and treatments. The consortium found that the eyesalve was capable of killing MRSA, a discovery that generated a lot of media attention and sparked expanded research efforts. The group brought data scientists and mathematicians into the consortium (work driven by Dr. Erin Connelly from the University of Warwick). Together, the researchers began scouring early modern and medieval texts and turning them into databases. The goal? To mathematically data mine these recipes see which ingredients were very often or non-randomly combined in ancient medical remedies. The group recently published work showing synergistic antimicrobial effects of acetic acid and honey. They are also working to pull out the active compounds from Bald’s eyesalve and make a synthetic cocktail that could be added to a wound dressings. A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity . Medieval medicine : the return to maggots and leeches to treat ailments. A case study of the Ancientbiotics collaboration . Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers . Sweet and sour synergy: exploring the antibacterial and antibiofilm activity of acetic acid and vinegar combined with medical-grade honeys.
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
Sending Yeast to the Moon With Jessica Lee
2023/05/05
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Dr. Jessica Lee, scientist for the Space Biosciences Research Branch at NASA’s AIMS Research Center in Silicon Valley uses both wet-lab experimentation and computational modeling to understand what microbes really experience when they come to space with humans. She discusses space microbiology, food safety and microbial food production in space and the impacts of microgravity and extreme radiation when sending Saccharomyces cerevisiae to the moon.
Ashley's Biggest Takeaways Lee applied for her job at NASA in 2020. Prior to her current position, she completed 2 postdocs and spent time researching how microbes respond to stress at a population level and understanding diversity in microbial populations. She has a background in microbial ecology, evolution and bioinformatics. Model organisms are favored for space research because they reduce risk, maximize the science return and organisms that are well understood are more easily funded. Unsurprisingly, most space research does not actually take place in space, because it is difficult to experiment in space. Which means space conditions must be replicated on Earth. This may be accomplished using creative experimental designs in the wet-lab, as well as using computational modeling. Links for the Episode: Out of This World: Microbes in Space. Register for ASM Microbe 2023 . Add “The Math of Microbes: Computational and Mathematical Modeling of Microbial Systems ,” to your ASM Microbe agenda.
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
Invisible Extinction: The Loss of Our Microbes with Maria Gloria Dominguez-Bello and Martin Blaser
2023/04/13
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Dr. Maria Gloria Dominguez-Bello, Henry Rutgers Professor of Microbiome and Health and director of the Rutgers-based New Jersey Institute for Food, Nutrition and Health, and Dr. Martin Blaser, Professor of Medicine and Pathology and Laboratory Medicine and director of the Center for Advanced Biotechnology and Medicine at Rutgers (NJ) discuss the importance of preserving microbial diversity in the human microbiome.
The pair, whose research was recently featured in a documentary The Invisible Extinction, are on a race to prevent the loss of ancestral microbes and save the bacteria that contribute to human health and well-being.
Links for the Episode: The Invisible Extinction (documentary) Missing Microbes (book) Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (article) (YouTube) Missing Microbes with Dr. Martin Blaser
The Self-Experimentation of Barry Marshall
2023/02/07
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Dr. Robert Gaynes, distinguished physician and professor of infectious diseases at Emory University, joins Meet the Microbiologist for the 3rd , and final, episode in a unique 3-part segment, in which we share stories about the life and work of medial pioneers in infectious diseases. Here we discuss the career of Dr. Barry Marshall, the Australian physician who is best known for demonstrating in a rather unorthodox way that peptic ulcers are caused by the bacterium, Helicobacter pylori .
Gaynes is author of Germ Theory: Medical Pioneers in Infectious Diseases , the 2nd edition of which will publish in Spring 2023. All 3 scientists highlighted in this special MTM segment are also featured in the upcoming edition of the book.
The Career of Tony Fauci
2022/12/22
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Dr. Robert Gaynes, distinguished physician and professor of infectious diseases at Emory University, joins Meet the Microbiologist for the 2nd episode in a unique 3-part series, in which we share the impact of scientists at the heart of various paradigm shifts throughout scientific history. Here we discuss the life and career of Tony Fauci, the scientist who has been recognized as America’s Top Infectious Diseases Doctor and “voice of science” during the COVID-19 pandemic.
Ashley's Biggest Takeaways Fauci was born in Brooklyn, New York. He was a 2nd generation American whose parents came from Italy. Fauci’s father was a pharmacist in Brooklyn and was very influential in his life. During high school, Fauci worked behind the counter at the family pharmacy and even delivered prescriptions by bicycle. He attended a Jesuit high school in Manhattan, and attended the College of Holy Cross. After college, Fauci attended Cornell Medical School in Manhattan, which was his first choice of medical school. Fauci graduated first in his class in medical school in the mid 1960’s, right in the midst of the Vietnam War. During that time, after completing their initial residency training, virtually all doctors were drafted into one of the military services or the U.S. Public Health Service. Fauci accepted into the NIH program within the U.S. Public Health Service, where he acquired training and a fellowship in Clinical Immunology and Infectious Diseases. Fauci became the Director of the National Institute of Allergy and Infectious Disease (NIAID) in 1984. Fauci served as advisor to 7 U.S. presidents, including Ronald Regan, George H.W. Bush, Bill Clinton, George W. Bush, Barack Obama, Donald Trump and Joe Biden. 15 years after the creation of PEPFAR, Fauci reported, in the New England Journal of Medicine, that PEPFAR funded programs had provided antiretroviral therapy to 13.3 M people, averted 2.2 M perinatal HIV infections and provided care for more than 6.4 M orphans and vulnerable children.
The first edition of "Germ Theory: Medical Pioneers in Infectious Diseases" is available now. The 2nd edition will publish in the spring of 2023.
Françoise Barré-Sinoussi's Discovery of HIV
2022/11/19
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Dr. Robert Gaynes, distinguished physician and professor of infectious diseases at Emory University, joins Meet the Microbiologist for a unique episode, in which we share the story of Françoise Barré-Sinoussi, the French, female scientist who discovered HIV and found herself at the heart of one of the most bitter scientific disputes in recent history.
Subscribe (free) on Apple Podcasts , Spotify , Google Podcasts , Android , RSS or by email .
Ashley's Biggest Takeaways The U.S. Centers for Disease Control and Prevention (CDC)’s Morbidity and Mortality Weekly Report first reported on a cluster of unusual infections in June of 1981, which would become known as AIDS. Evidence suggested that the disease was sexually transmitted and could be transferred via contaminated blood supply and products, as well as contaminated needles, and could be passed from mother to child. All hemophiliacs of this generation acquired AIDS (15,000 in the U.S. alone). The fact that the microbe was small enough to evade filters used to screen the clotting factor given to hemophiliacs indicated that the etiologic agent was a virus. AIDS patients had low counts of T-lymphocytes called CD4 cells. By 1993, the most likely virus candidates included, a relative of hepatitis B virus, some kind of herpes virus or a retrovirus. Howard Temin discovered reverse transcriptase, working with Rous sarcoma in the 50s and 60s. His work upset the Central Dogma of Genetics, and at first people not only did not believe him, but also ridiculed him for this claim. Research conducted by David Baltimore validated Temin’s work, and Temin, Baltimore and Renato Dulbecco shared the Nobel Prize for the discovery in 1975. Robert Gallo of the U.S. National Institute of Health (NIH), discovered the first example of a human retrovirus—human T-cell lymphotropic virus (HTLV-1). Françoise Barré-Sinoussi worked on murine retroviruses in a laboratory unit run by Luc Montagnier, where she became very good at isolating retroviruses from culture. In 1982, doctors gave lab Montagnier’s lab a sample taken from a with generalized adenopathy, a syndrome that was a precursor to AIDS. Barré-Sinoussi began to detect evidence of reverse transcriptase in cell culture 2 days after the samples were brought to her lab. Barré-Sinoussi and Luc Montagnier were recognized for the discovery of HIV with the 2008 Nobel Prize in Physiology or Medicine. Links for the Episode:
From the ancient worlds of Hippocrates and Avicenna to the early 20th century hospitals of Paul Ehrlich and Lillian Wald to the modern-day laboratories of François Barré-Sinoussi and Barry Marshall, Germ Theory brings to life the inspiring stories of medical pioneers whose work helped change the very fabric of our understanding of how we think about and treat infectious diseases.
Germ Theory: Medical Pioneers in Infectious Diseases
The second edition of Germ Theory , which will include chapters on Françoise Barré-Sinoussi, Barry Marshall and Tony Fauci, will publish in Spring 2023.
Permafrost with Devin Drown
2022/10/28
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Dr. Devin Drown, associate professor of biology and faculty director of the Institute of Arctic Biology Genomics Core at the University of Alaska Fairbanks, discusses how soil disturbance gradients in the permafrost layer impact microbial communities. He also explains the larger impacts of his research on local plant, animal and human populations, and shares his experience surveilling SARS-CoV-2 variants in Alaska, where he and colleagues have observed a repeat pattern of founder events in the state.
Ashley's Biggest Takeaways Permafrost is loosely defined as soil that has been frozen for 2 or more years in a row. Some permafrost can be quite young, but a lot of it is much older—1000s of years old. This frozen soil possesses large storage capacity for walking carbon and other kinds of nutrients that can be metabolized by microbes as well as other organisms living above the frozen ground. About 85% of the landmass in Alaska is underlined by permafrost. Some is continuous permafrost, while other areas of landmass are discontinuous permafrost—locations where both unfrozen soil and frozen soil are present. As this frozen resource is thawing as a result of climate change, it is releasing carbon and changing soil hydrology and nutrient composition, in the active layer in the soil surrounding it. Changes in the nutrients and availability of those nutrients are also likely changing the structure of the microbial communities. Drown and team are using a combination of traditional (amplicon sequencing) and 3rd generation (nanopore) next sequencing (NGS) techniques to characterize the microbes and genes that are in thawing permafrost soil. Featured Quotes: “Globally, we've seen temperatures increase here in the Arctic. Changes in global temperatures are rising even faster, 2-3 times, and I've heard recent estimates that are even higher than that.”
“These large changes in temperatures are causing direct impacts on the thaw of the permafrost. But they're also generating changes in other patterns, like increases in wildfires. We just had a substantial wildfire season here in Alaska, and those wildfires certainly contribute to additional permafrost thaw by sometimes removing that insulating layer of soil that might keep that ground frozen, as well as directly adding heat to the to the soil.”
“There are other changes that might be causing permafrost thaw, like anthropogenic changes, changes in land use patterns. As we build and develop roads into areas that haven't been touched by humans in a long time. We're seeing changes in disruption to permafrost.”
“Some people are quite interested in what might be coming out of the permafrost. We might see nutrients, as well as microorganisms that are moving from this frozen bank of soil into the active layer.”
“We're using next generation sequencing techniques to characterize not only who is in these soils, but also what they're doing.”
“I started as a faculty member in 2015. As I moved up to Alaska, I got some really great advice from a postdoctoral mentor that said, make sure you choose something local. I'm fortunate enough that I have access to permafrost thaw gradient, that's effectively in the backyard of my office.”
“Just a few miles from campus, we have access to a site that's managed by the Army Corps of Engineers. They have a cold regions group up here that runs a more famous permafrost tunnel. So they've dug a deep tunnel into the side of a hill that stretches back about 40,000 years into permafrost. They also have a great field site that has an artificially induced permafrost thaw gradient, and a majority of our published work has been generated by taking soil cores from that field site.”
“Maintaining that cold chain, whether it’s experimental reagents or experimental samples, is a challenge for everyone. We're collecting active layer soil—the soil directly beneath our feet—so that's not at terribly extreme temperatures. But we do put it in coolers immediately upon extracting from the from the environment. Then we can bring it back to our lab where we can freeze it if we're going to use it for later analysis, or we can keep it at appropriately cool temperatures, if we're going to be working with the microbial community directly.”
“We were most interested in looking for microbes that might have impacts on the above ground. ecosystem. So when we were characterizing the microbial community, we were doing that because we also wanted to link it to above ground changes.”
“Changes in vegetation that might be driven by changes in microorganisms would certainly have an impact on the wildlife that are that are present at the site. So, just as an example, if we see a decrease in berries that might be present, that might decrease the interest from animals that rely on that [food source]. And so we might see changes in who's there.”
“Outside of my research, we've seen changes in the types of plants present across northern latitudes. So different willows, for instance, are moving farther north, and that is leading animals, like moose, to move farther north. And so we might see changes in those kinds of patterns directly as a result of the microorganisms as well.”
“We're really working to expand our efforts to move to other kinds of disturbances. I mentioned wildfires before, these are an important source of disturbance for boreal forest ecosystems. We have a project here in the interior, looking at the impacts of wildfires on microbial communities and how [these disturbances] might be changing the functional potential of microbial communities.”
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
To Catch a Virus with Marie Landry and John Booss
2022/10/17
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Dr. Marie Landry, Professor of Laboratory medicine and Infectious Diseases at Yale University School of Medicine and Dr. John Booss, former National Director of Neurology for the Department of Veteran’s Affairs discuss the past, present and future of diagnostic virology. These proclaimed coauthors walk us through the impact of some of the most significant pathogens of our time in preparation for the launch of their 2nd edition of “To Catch a Virus,” a book that recounts the history of viral epidemics from the late 1800s to present in a gripping storytelling fashion.
Ashley's Biggest Takeaways Coauthoring a book requires having great respect for the opinions of the person you are working with. The first human disease shown to be viral in nature was yellow fever, but for quite some time, the mode of disease transmission remained mysterious. In early 1881, Carlos Finlay of Cuba suggested that the disease could be spread by mosquitoes and significantly advanced the field. It wasn’t until polio was discovered in the early 1900s that scientists determined that viruses could also be transmitted by and animals. The ability to grow virus in tissue culture was another huge advancement in the field of diagnostic virology, which eventually led to the development of the Salk inactivated polio vaccine (IPV). Although he did not seek the spotlight for his work, Walter Roe, was a bright, hardworking (and one of John’s favorite) virologist, who made important advances in tissue culture, researched the role of retroviruses in animal cancer and discovered adenoviruses. As a result of the COVID-19 pandemic, the clinical laboratory played a central role in public health. The importance of a laboratory diagnosis became more evident and next generation sequencing moved further into the clinical lab. Featured Quotes: “Advice that was given to me way back when I started on my first book is that you have to write about something you're passionate about. You have to really believe in the topic because otherwise it'll come across as superficial and artificial. So the very first step is do you really believe in, [and in the case of writing a book, that means] believe in what you're writing about.” – Booss.
“Science is often projected as a steady stream of advances one after the other. But there is a certain amount, I think, of arbitrary choice at each step. And it's also true for for writing a book.” – Booss
“In putting the book together, there are obviously major events that occurred in virology, major crises that move the field forward, an interplay, really, of the scientific advances, the clinical need of the crisis at hand and some very remarkable people. One highlight of this book is the way it does focus on individuals and their stories and how they contributed to that progress.” -Landry
“When [pathogens] spread from a local area to a larger area geopolitical area or even globally, they become pandemic.” Polio “The most compelling virus that I can think of in my youth was obviously polio. So when I was a small child, polio was causing epidemics every summer, at the end of which, between 20 and 30,000 children in the United States were left either paralyzed or dead. So this was it really struck fear into parents hearts.” – Landry
“And then came the oral polio vaccine. We lined up, and it was a very, very painless way to be immunized. So that was a tremendous success story, we've come very close to eliminating polio, because of a number of reasons it hasn't happened.” - Landry
“There was a case recently of paralytic polio in New York, in an unvaccinated person. And I hope this is a wake-up call, we really thought we were about to eliminate before COVID. And then with those disruptions and others, there's been a little resurgence, but I hope that it will be accomplished soon.” -Landry COVID-19 “It's amazing how much the world did change. International economies collapsed. whole societies shut down. The education and socialization of children came to a screeching halt. As schools close, whole chasms of inequality opened up or were revealed. And also the poor and marginalized people were the ones who suffered most. And the U.S. cultural divisions interfered with attempts to block the disease. So that by 2022, the U.S. was unique in having over 1 million deaths. We lead unfortunately led the world in that regard.” – Booss
“Sometimes we need a crisis to move us forward. And we saw this with the new vaccine platforms, especially the mRNA vaccine.”
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan . Links From yellow fever and smallpox, to polio, AIDS and COVID-19, To Catch a Virus guides readers through the mysterious process of catching novel viruses and controlling deadly viral epidemics— and the detective work of those determined to identify the culprits and treat the infected.
The new edition will be released October 15, 2022, available at asm.org/books
Outbreak Detection with Wun-Ju Shieh
2022/10/01
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Dr. Wun-Ju Shieh, worked as a pathologist and infectious diseases expert with the CDC from 1995-2020. He recounts his experiences conducting high risk autopsies on the frontlines of outbreaks including Ebola, H1N1 influenza, monkeypox and SARS-CoV-1 and 2. He also addresses key questions about factors contributing to the (re)emergence and spread of pathogens and discusses whether outbreaks are becoming more frequent or simply more widely publicized.
Ashley’s Biggest Takeaways:
• Pathologists are a group of medical doctors serving behind the line of the daily hospital activities.
• Pathology service can be divided into atomic pathology and clinical pathology. The field covers all the laboratory diagnostic work in the hospital, and clinical microbiology or medical microbiology is actually a subdivision within the clinical pathology service.
• Usually, a pathologist working in a hospital will examine and dissect tissue specimens from surgery or biopsy.
• The pathologist also performs autopsies as requested to determine or confirm the cause of death.
• Serving as first a clinician in Taiwan and then a pathologist in the United States has provided Shieh with the unique experience of evaluating patients from both the outside-in and the inside-out!
• Even when a major outbreak of a known etiologic agent is taking place, confirmatory diagnosis is necessary for subsequent quarantine, control and prevention of the outbreak.
• During major disease outbreaks, other pathogens do not go away, and we must simultaneously facilitate their timely diagnosis to ensure effective patient treatment and care.
• SARS-CoV-2 appears to be transmitted more easily than SARS-CoV-1. One possible explanation for this is that the amount of viral load appears to be the highest in the upper respiratory tract of those with COVID-19, shortly after the symptoms develop. This indicates that people with COVID-19 may be transmitting the virus early in infection, just as their symptoms are developing…or even before they appear or without symptoms.
• SARS-CoV-1 viral loads peak much later in the illness.
• Asymptomatic transmission is rarely seen with SARS-CoV-1 infection.
• Almost 99% of SARS-CoV-1 patients developed prominent fever when they started to carry infectivity. Temperature monitoring was therefore, very effective at detecting sick patients and facilitating prompt quarantining procedures, which effectively contained/minimized transmission of the virus.
• This was not as effective for SARS-CoV-2, despite early attempts at temperature. monitoring.
• SARS-CoV-2 was much harder to contain both because of the milder display of host symptoms and the demonstration of higher viral transmissibility.
Lyme Disease Prevention and Treatment with Linden Hu
2022/09/02
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Dr. Linden Hu, Vice Dean for Research at Tufts University in Boston Massachusetts and Paul and Elaine Chervinsky Professor in Immunology, discusses new and ongoing research pertaining to the prevention, treatment and diagnosis of human Lyme disease. He also discusses some of the key unanswered questions about Lyme, such as how B. burgdorferi adapts to different hosts and environments and why some patients have been known to exhibit persistent symptoms even after treatment.
Links mentioned:
Webinar - Vector-Borne Disease in a Changing Climate https://asm.org/Webinars/Vector-Borne-Disease-in-a-Changing-Climate The Bulls-Eye Rash of Lyme Disease: https://asm.org/Articles/2018/April/going-skin-deep-investigating-the-cutaneous-host-p Pfizer and Valneva Initiate Phase 3 Study of Lyme Disease Vaccine Candidate VLA15 https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-valneva-initiate-phase-3-study-lyme-disease Could This Treatment Prevent Chronic Lyme Disease? https://news.northeastern.edu/2021/10/06/preventing-chronic-lyme-disease/ Promising New Drug Would Eradicate Lyme While Leaving Gut Microbes Alone: https://www.lymedisease.org/members/lyme-times/2022-spring-news/targeted-lyme-disease-drug/ A Tick’s Meal: https://asm.org/Podcasts/TWiM/Episodes/A-Tick-s-Meal-TWiM-258 Evidence That the Variable Regions of the Central Domain of VlsE Are Antigenic during Infection with Lyme Disease Spirochetes https://journals.asm.org/doi/10.1128/IAI.70.8.4196-4203.2002 Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis of Borrelia burgdorferi and Cytokine Induction https://journals.asm.org/doi/10.1128/IAI.01600-07
Tardigrades and Microbial Midwives with Mark O. Martin
2022/08/08
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Dr. Mark O. Martin, Associate professor of biology at the University of Puget Sound in Tacoma, Washington is a distinguished educator with a well-known social media presence. He discusses how he became interested in microbiology and what drives his varied research foci, including #Microbialcentricity, bacterial predation, bioluminescence, tardigrades, microbial midwives and more. In the process, he delves into his passion for using art and other creative approaches to facilitate learning in the classroom, and shares some experience-driven wisdom about building confidence in STEM.
Links for this Episode:
Vertically transmitted microbiome protects eggs from fungal infection and egg failure https://animalmicrobiome.biomedcentral.com/articles/10.1186/s42523-021-00104-5 The effects of Sceloporus virgatus cloacal microbiota on the growth of pathogenic fungi https://soundideas.pugetsound.edu/summer_research/426/ Sex-specific asymmetry within the cloacal microbiota of the striped plateau lizard, Sceloporus virgatus https://link.springer.com/article/10.1007/s13199-010-0078-y Predatory Prokaryotes: An Emerging Research
Opportunity (pdf) https://www.pugetsound.edu/sites/default/files/file/martin2002_0.pdf Carleton College #LuxArt 2019 https://www.youtube.com/watch?v=fztiJ3o7uWs
Shark Epidermis Microbiome with Elizabeth Dinsdale
2022/05/20
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Dr. Elizabeth Dinsdale, Matthew Flinders Fellow in Marine Biology in the College of Science and Engineering at Flinders University in Adelaide, Australia, uses genomic techniques to investigate the biodiversity of microbial communities in distinct ecological niches, including coral reefs, kelp forest and shark epidermis. She discusses how shotgun metagenomics is being used to characterize the architecture of microbial communities living in the thin layer of underlying mucus on shark’s skin, and how understanding the function of these microbes is providing clues to important host-microbe interactions, including heavy metal tolerance.
Ashley’s Biggest Takeaways:
Sharks belong to a subclass of cartilaginous fish called elasmobranchs and are unique in that their epidermises are covered in dermal denticles—overlapping tooth-like structures that reduce drag and turbulence, helping the shark to move quickly and quietly through the water. These dermal denticles are sharp (if you’re going to pet a shark, make sure you go from the head to the tail to avoid getting cut!), and depending on the species of shark, may be more or less spread out across the epidermis.
Where do microbes enter the story? Dermal denticles overlay a thin layer of mucus, which provides a distinctive environment for microbial life. Collecting microbial samples from underneath a shark’s dermal denticles is quite difficult, and the technique varies by shark species (shark size, water depth and ability to bite all factor into the equation). Liz’s team uses a specially designed tool that the group affectionately calls a “supersucker,” to create and capture a slurry of microbes and water for analysis.
The team then uses shotgun metagenomics to identify and characterize the microbes in their collected samples. Sequencing has revealed biogeographical difference, as well as similarities in microbial architecture of whale sharks across the globe.
There are 2 populations of whale sharks—one in the Atlantic Ocean and the other in the Indian Pacific Ocean. Samples collected from both populations have revealed that each individual whale shark, from within each aggregation, shares many of the same microbes. In fact, unlike algae which may share 1 to 2 microbial species, whale sharks share about 80% of microbes across every individual. Since many of the sharks don’t cross aggregations, Liz’s team is investigating the possibility of coevolution between microbes and hosts.
Metagenomic sequencing also provides information about the function of the sequenced microbes. High presence of heavy metal-tolerant microbes has been found in the epidermis of all shark species that the team has analyzed. Sharks are known to carry high levels of heavy metals in their skin, muscle and even blood. However, muscle tissue samples contain lower concentrations than skin, indicating that there may be a density gradient in place, and raising questions about how microbes might be involved in this regulation. Is there a pathway by which the microbes metabolize and help to remove concentrations of heavy metals across the epidermis? Liz and her team are hoping to find out.
Links:
Elizabeth Dinsdale https://www.flinders.edu.au/people/elizabeth.dinsdale Tracking Pathogens via Next Generation Sequencing (NGS) https://asm.org/Magazine/2021/Spring/Tracking-Pathogens-via-Next-Generation-Sequencing Microbial Ecology of Four Coral Atolls in the Northern Line Islands https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001584 Coral Research https://coralandphage.org/research_coral.php Metagenomic analysis of stressed coral holobionts https://pubmed.ncbi.nlm.nih.gov/19397678/ Metagenomic analysis of the microbial community associated with the coral Porites astreoides https://pubmed.ncbi.nlm.nih.gov/17922755/
Microbial Culture Collections and the Soil Microbiome with Mallory Choudoir
2022/04/18
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Dr. Mallory Choudoir, microbial ecologist and evolutionary biologist at the University of Massachusetts Amherst shares how she leverages microbial culture collections to infer ecological and evolutionary responses to warming soil temperatures. She discusses complexities of the soil microbiome and microbial dispersal dynamics, and introduces fundamental concepts about the intersection between microbes and social equity.
Ashley’s Biggest Takeaways:
Microbial culture collections are fundamental resources, serving as libraries where diverse species of microbes are identified, characterized and preserved in pure, viable form. Culture collections ensure conservation of species diversity and sustainable use of the collected microbes.
For soil microbiologists, like Mallory Choudoir, culture collections provide the opportunity to connect patterns of genomic variation and microbial physiology to the conditions under which a particular microbe was isolated.
Soil is a complex environment from the perspective of a microbe. In order to coexist in such a biologically diverse environment, which consists of spatial heterogeneity, as well as heterogeneity in access to moisture and nutrients, microbes must evolve different strategies to survive as part of a stable community.
Choudoir’s field site is based in the Harvard Forest Long Term Ecological Research Program's field site, where coils are buried and have been heating the forest soil to 5 degrees above ambient temperatures for nearly 30 years. The study allows Choudoir and colleagues to observe and evaluate long-term responses to chronic soil warming stress.
This research is important because microbes function as resources to the health and well-being of ourselves and our planet. Understanding how microbes adapt to biotic and abiotic stresses can help inform future conservation strategies, biotechnological approaches and applications and equitable allocation of microbial resources.
Visit https://asm.org/mtm for links mentioned
Neglected Tropical Diseases and Pandemic Prevention With Peter Hotez
2021/11/01
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Peter Hotez talks about the global impact and historical context of neglected tropical diseases. He also highlights important developments in mass drug administration and vaccine research and shares why he chose to publish the third edition of Forgotten People, Forgotten Diseases during the COVID-19 pandemic.
Ashley's Biggest Takeaways
Neglected Tropical Diseases (NTDs) are chronic and debilitating conditions that disproportionately impact people in low- and middle-income countries (LMICs).
Many of these diseases are parasitic, such as hookworm infection, schistosomiasis and chagas disease; however, in recent years, several non-parasitic infections caused by bacteria, fungi and viruses, as well as a few conditions that are not infections, including snake bite and scabies (an ectoparasitic infestation), have been added to the original NTD framework (established in the early 2000s).
What do most NTDs have in common?
High prevalence.
High mortality; low morbidity.
Disabling.
Interfere with people’s ability to work productively.
Impact child development and/or the health of girls and women.
Occur in a setting of poverty and actually cause poverty because of chronic and debilitating effects.
Hotez and his colleagues recognized that there is a uniqueness to the NTDs ecosystem, and they began putting together a package of medicines that could be given on a yearly or twice per year basis, using a strategy called Mass Drug Administration (MDA). This involved the identification of medicines that were being used on an annual basis in vertical control programs and combining those medications in a package of interventions that costs about $0.50 per person per year. “Throw in an extra 50 cents per person and we could double or triple the impact of public health interventions,” he explained.
Emerging diseases, such as SARS-CoV-2, capture the attention of the public for obvious reasons. They pose an imminent threat to mankind. NTDs are not emerging infections, but they are ancient afflictions that have plagued humankind for centuries and, as a consequence, have had a huge impact on ancient and modern history. One of the reasons we have mainland China and Taiwan today may have been, in part, due to a parasitic infection, Schistosomiasis.
Hotez and colleagues at the Texas Children’s Center for Vaccine Development have developed a COVID-19 vaccine, based on simple technology, similar to what is used for the Hepatitis B vaccine. They hope to release the vaccine for emergency use in resource poor countries like India and Indonesia.
When asked about the timing of the publication of his book, the third edition of Forgotten People, Forgotten Diseases, Hotez acknowledged the difficulty of helping countries understand that NTDs have not gone away. COVID-19 is superimposed on top of them, and the pandemic has done a lot of damage in terms of NTD control. Although social disruption has interfered with the ability to deliver mass treatments, Hotez said that it has been gratifying to see that the USAID and their contractors have responded by putting out guidelines about how to deliver mass treatments with safe social distancing.
“As a global society, we have to figure out how to walk and chew gum at the same time,” he said. “We’ve got to take care of COVID, but we really must not lose the momentum we’ve had for NTDs because the prevalence is starting to decline and we’re really starting to make an impact.”
133: Vibrio cholerae with Rita Colwell
2021/06/10
Rita Colwell has made major advances in basic and applied microbiology, largely focused on Vibrio cholerae . She describes several lines of evidence for the environmental niche of the bacterium, as well as her work to predict and prepare for cholera outbreaks. Colwell closes with her thoughts on why it’s a great time to be a microbiologist.
132: Life Science and Earth Science and Biogeomicrobiology with Denise Akob
2020/11/12
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Denise Akob discusses her studies of microbial communities of contaminated and pristine environments using life science and earth science techniques. She discusses how to figure out “who’s there,” how to optimize select natural microbial activities, and her career path into government research.
Julie’s Biggest Takeaways:
Biogeomicrobiology straddles the life science and earth science fields. This is a growing area of research in the academic setting as well as in the private sector, where one can contribute to hydrogeology or bioremediation efforts.
What happens on the surface when extracting resources like natural gases? Wastewater from hydraulic shale fracking, or fracking, can contaminate microbes. Preliminary data suggests that microbes that thrive in that wastewater can be a fingerprint for surface contamination, and this is one of the areas of active research in Akob’s lab. Additionally, microbes can respond to contaminants to remove that risk and remediate the spills.
One trip to the field can provide samples for years of analysis. From one sample, scientists can conduct:
Microbiome studies through amplicon sequencing to understand population structures. Metagenomics studies to understand functional potential. Biochemical studies to understand active metabolic processes.
Akob asks how to make natural microbial degraders happy. For example: acetylene, a triple-bonded carbon compound, can inhibit degradation of chlorinated solvents, a potent groundwater contaminant. By studying the microbes that use acetylene as a primary energy source (acetylenotrophs), this removes this inhibition caused by acetylene and the chlorinated solvent-degraders can increase their activity.
Akob studies pristine environments to understand natural microbial communities. A cave she studied in Germany was ‘ultra pristine,’ discovered while building a highway. Understanding natural processes, such as the biomineralization promoted during stalagmite and stalactite formation helps scientists imagine how to use tehse processes in other applications.
Links for this Episode:
Mumford AC et al . Common Hydraulic Fracturing Fluid Additives Alter the Structure and Function of Anaerobic Microbial Communities. Applied and Environmetnal Microbiology. 2018. Akob DM et al . Acetylenotrophy: a Hidden but Ubiquitous Microbial Metabolism? FEMS Microbial Ecology . 2018. Akob DM et al . Detection of Diazotrophy in the Acetylene-Fermenting Anaerobic Pelobacter sp. Strain SFB93. Applied and Environmental Microbiology. 2017. ASM Article: The Microbial World of Caves James J, Gunn AL, and Akob DM. Binning Singletons: Mentoring through Networking at ASM Microbe 2019. mSphere. 2020. HOM Tidbit: Scientists Find Ancient Cave Dwelling Resistant Bacteria ASM Press: Women in Microbiology
131: Powassan virus and tick biology with Marshall Bloom
2020/07/31
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How does tick biology influence their ability to transmit disease? Marshall Bloom explains the role of the tick salivary glands in Powassan virus transmission and the experiments that led to this discovery. He also provides a historical background for the Rocky Mountain Labs in Hamilton, Montana, and talks about the 3 elements to consider when working with potentially harmful biological agents.
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Julie’s Biggest Takeaways
There are 3 elements to consider when working with potentially harmful biological agents:
Biosafety: protecting the laboratory workers from the infectious agents in the lab.
Biocontainment: protecting the community by keeping the infectious agent contained within the facility.
Bioassurity: protecting the individual by ensuring those working with infectious agents are capable to do so.
You need 4 bites of an APPLE for full lab safety, for work in labs from high school level through biosafety level 4:
A: Administration. Training, paperwork, etc. P: Personal protective equipment (PPE). Varies from gloves to positive pressure suits, depending on the microorganisms under study. PL: Laboratory procedures. Standard operating protocols. E: Engineering. Biosafety cabinets and labs that have protective features.
Most of the vector-borne flaviviruses, including Powassan virus, don’t cause overt disease in the people they infect, so many people never know they’ve been infected. Without serological surveys, it’s difficult to know the full range of infected individuals versus those that develop serious disease. Serious disease often manifests in neurological symptoms such as encephalitis, with 10-15% mortality rate; half of those suffering neurological disease will continue to have serious sequelae for years.
The Rocky Mountain Labs was once the world reference center for ticks: it held thousands of samples which represented the type species for the entire world.
The tick salivary glands look like a bunch of grapes: the stem of the grapes is a series of branching ducts. The “grapes” at the end of the ducts are the acini, which is Latin for ‘little sac.’ These acini play a major role in tick feeding, and different types of acini play different functional roles:
Type 1 acini: cells have no granules. Acini involved with fluid exchange. Type 2 and type 3 acini: cells with granules. Cells degranulate to release vasoactive compounds into tick saliva during feeding. Featured Quotes
“The first isolation of Powassan virus was from a little boy in Powassan, Canada in 1958. If you look at the cases over the years, the numbers are going up, but compared to Lyme disease, they’re pretty low: there’s been less than 200 cases, all told.”
“Amazingly, the Powassan virus can be transmitted in as little as 15 minutes….[and] a female tick can take days to get a full meal.”
“I take a tick-centric view. If I can anthropomorphize, as my old friend Stanley Falkow used to say, he’d say ‘think like the microbe.’ The microbe doesn’t really care if we get sick or not. The microbe is just trying to make a living and survive.”
“One of the really surprising things is that infected ticks can infect uninfected ticks, if they are feeding right next to each other. Ticks like to feed in groups: it’s called co-feeding. The virus can transferred really quickly, 15 min, which is way faster than the virus can go through a replication cycle. What that means to me is that the ticks are infecting each other….we want to investigate the role of co-feeding.”
“If something sounds like fun or sounds important, and especially if something sounds fun AND important, then you should do it.”
Links for this Episode:
Paules CI et al . Tickborne Diseases--Confronting a Growing Threat. New England Journal of Medicine . August 2018.
Amazon: Fighting Spotted Fever in the Rockies by Esther Gaskins Price
New York Times: Kay Hagan obituary
Grabowski JM et al . Dissecting Flavivirus Biology in Salivary Gland Cultures from Fed and Unfed Ixodes scapularis (Black-Legged Tick). mBio . January 2019.
ASM on Instagram
Grabowski JM, Offerdahl DK, and Bloom ME. The Use of Ex Vivo Organ Cultures in Tick-Borne Virus Research. ACS Infectious Disease. Marhc 2018.
Twitter thread from @BugQuestions: Rocky Mountain Spotted Fever and Howard Ricketts History of Microbiology Tidbit: A Short History of the Screwworm Program
130: Bioremediation of oil spills with Joel Kostka
2020/05/19
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What kinds of microorganisms can degrade oil? How do scientists prioritize ecosystems for bioremediation after an oil spill? Joel Kostka discusses his research and the lessons from the Deepwater Horizon oil spill that will help scientists be better prepared for oil spills of the future.
Links for this Episode:
Joel Kostka Lab Website Kostka J. et al . Hydrocarbon-Degrading Bacteria and the Bacterial Community Response in Gulf of Mexico Beach Sands Impacted by the Deepwater Horizon Oil Spill. Applied and Environmental Microbiology . 2011. Shin B. et al . Succession of Microbial Populations and Nitroget-Fixation Associated With the Biodegradation of Sediment-Oil-Agglomerates Buried in a Florida Sandy Beach. Scientific Reports . 2019. Bociu I. Decomposition of Sediment-Oil-Agglomerates in a Gulf of Mexico Sandy Beach. Scientific Reports . 2019. Overhold W.A. et al . Draft Genome Sequences for Oil-Degrading Bacterial Strains from Beach Sands Impacted by the Deepwater Horizon Oil Spill. Genome Announcements . 2013. Gulf of Mexico Research Initiative ASM Colloquia Report: Microbial Genomics of the Global Ocean System ASM Article: Microbiomes: An Origin Story Joyful Microbe Blog: How to make a Winogradsky column
Small Things Considered: How to Build a Giant Winogradsky Column 20% off The Invisible ABCs for MTM listeners! Use promo code: ABC20 at checkout.
129: Arbovirus evolution with Greg Ebel
2020/04/23
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How do arboviruses evolve as they pass between different hosts? Greg Ebel discusses his research on West Nile virus evolution and what it means for viral diversity. He also talks about using mosquitos’ most recent blood meal to survey human health in a process called xenosurveillance.
Julie’s Biggest Takeaways:
Mosquitoes and other arthropods have limited means of immune defense against infection. One major defense mechanism is RNA interference (RNAi). RNAi uses pieces of the West Nile viral genome to select against the viral genome, which helps select for broadly diverse viral sequences. The more rare a viral genotype, the more likely it is to escape negative selection inside the mosquito host, allowing this viral sequence to increase in frequency.
West Nile virus passes largely between birds and mosquitos. Culex mosquitos tend to prefer birds, and this leads to an enzootic cycle for the virus passing between birds and mosquitos. The viral life cycle inside the mosquito has several important steps:
The virus first enters as part of the mosquito blood meal. The virus infects epithelial cells of the mosquito midgut. After 3-5 days, the virus leaves the midgut (midgut escape) to enter the mosquito hemolymph. In the next mosquito blood meal, virus is expelled with saliva, which has anticoagulant activity.
West Nile virus selection undergoes cycles of selection as it passes from vertebrates (mostly birds) to invertebrates (mosquitos):
In vertebrates, the virus must escape to cause viremia in a short period of time for replication to occur before the immune system recognizes and eliminates the virus. This leads to purifying selection, or elimination of amino acid variation that decreases viral protein function. In mosquitos, the virus spends several days in the midgut epithelial cells and then hemolymph, leading to a longer selection time. This leads to more viral diversity in the mosquito host. RNAi further drives population diversity. Through stochasticity, a single viral population will often come to dominate a single infected mosquito.
How do scientists know which virus replicates best? Competitive fitness tests measure which virus grows to a higher population in a given environment. A manipulated virus (one passaged in a mosquito or selectively mutated at distinct sequences) and its non-manipulated parent sequence are inoculated at known proportions, and given a certain amount of time to replicate. By measuring the final proportions, Greg and his team can determine which sequence was more fit in that given environment.
Xenosurveillance uses mosquitoes to detect a wide array of pathogens at clinically relevant levels. Testing began with in vitro blood-bag feeding, and was validated with studies in Liberia and Senegal. The microorganism sequences are so diverse that the information was used to identify novel human viruses. These studies also provide insight into mosquito feeding habits, which helps in disease modeling.
Links for this Episode:
Greg Ebel Lab Website Rückert C. et al. Small RNA Responses of Culex Mosquitoes and Cell Lines during Acute and Persistent Virus Infection. Insect Biochemistry and Molecular Biology. 2019. Grubaugh N.D. et al. Mosquitoes Transmit Unique West Nile Virus Populations during Each Feeding Episode. Cell Reports . 2017. Grubaugh N.D. and Ebel G.D. Dynamics of West Nile Virus Evolution in Mosquito Vectors. Current Opinion in Virology . 2016. Fauver J.R. et al . Xenosurveillance Reflects Traditional Sampling Techniques for the Identification of Human Pathogens: A Comparative Study in West Africa. PLoS Neglected Tropical Diseases . 2018. Fauver J.R. The Use of Xenosurveillance to Detect Human Bacteria, Parasites, and Viruses in Mosquito Bloodmeals. American Journal of Tropical Medicine and Hygiene . 2017. Tracey McNamera: Canaries in the Coal Mine TEDxUCLA New York Times: Encephalitis Outbreak Teaches an Old Lesson. 1999. ASM Article: The One Health of Animals, Humans, and Our Planet: It’s All Microbially Connected
128: Managing Plant Pathogens Using Streptomyces with Linda Kinkel
2020/03/26
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How can the intricate relationship between soil microbiota and plants be managed for improved plant health? Linda Kinkel discusses new insights into the plant rhizosphere and the ways that some Streptomyces isolates can protect agricultural crops against bacterial, fungal, oomycete, and nematode infections.
Julie’s Biggest Takeaways :
The soil microbiome is extremely dynamic, with boom-and-bust cycles driven by nutrient fluxes, microbial interactions, plant-driven microbial interactions, and signaling interactions. Finding the source of these boom-and-bust cycles can help people to manage the microbiome communities and produce plant-beneficial communities for agricultural purposes.
Rhizosphere soil is soil closely associated with the root and is distinct from rhizoplane soil that directly touches the root. The endophytic rhizosphere are those microbes that get inside the root. Many scientists view these communities as a continuum rather than sharply delineated.
Plants provide necessary carbon for the largely heterotrophic soil microbiota, and these microorganisms help the plants in several ways too:
Microbes mediate plant growth by production of plant growth hormones. Microbes provide nutrients through mechanisms like nitrogen fixation or phosphorus solubilization. Microbes protect the plant from stress or drought conditions.
Through a University of Minnesota plant pathology program, potatos were passaged in a field for over 2 decades to study potato diseases. Over time, researchers found fewer diseases in test crops, which led the plot to be abandoned in the late 1970s. In the 1980s, Dr. Neil Anderson planted potatoes to see if they would develop disease, but neither Verticillium wilt nor potato scab developed among the plants. Soil from the field (and on the potatoes) contained Streptomyces isolates that showed antimicrobial activity against bacteria, fungi, nematodes, and oomycetes. This discovery led Neil, new University of Minnesota professor Linda, and their collaborators to study the antimicrobial activity of natural Streptomyces isolates from around the world.
Inoculation quickly adds specific microbial lineages to soil microbiome communities. Alternatively, land can be managed by providing nutrients to encourage the growth of specific species, like Streptomyces , within a given plot, but this takes longer to develop. How are soil microbiomes inoculated? Microbes can be:
Added to the seed coating before planting. Placed in the furrow when the seed is planted. Distributed into the irrigation system.
Links for this Episode :
Linda Kinkel website at University of Minnesota Essarioui A. et al . Inhibitory and Nutrient Use Phenotypes Among Coexisting Fusarium and Streptomyces Populations Suggest Local Coevolutionary Interactions in Soil. Environmental Microbiology . 2020. Schlatter D.C. et al . Inhibitory Interaction Networks Among Coevolved Streptomyces Populations from Prairie Soils. PLoS One . 2019. Schlatter D.C. et al . Resource Use of Soilborne Streptomyces Varies with Location, Phylogeny, and Nitrogen Amendment. Microbial Ecology . 2013. Small Things Considered blog: Are Oomycetes Fungi or What? International Year of Plant Health HOM Tidbit: Austin-Bourke P.M. Emergence of Potato Blight, 1843-1846. Nature . 1965.
127: E. coli and Burkholderia vaccines with Alfredo Torres
2020/03/02
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Pathogenic E. coli are different than lab-grown or commensal E. coli found in the gut microbiome. Alfredo Torres describes the difference between these, the method his lab is using the develop vaccines against pathogenic E. coli , and how this same method can be used to develop vaccines against Burkholderia infections.
Julie’s Biggest Takeaways:
coli plays many roles inside and outside the scientific laboratory: Laboratory E. coli strains used by scientists to study molecular biology. Commensal E. coli strains contribute to digestion and health as part of the intestinal microbiome. Pathogenic E. coli strains have acquired factors that allow them to cause disease in people
The pathogenic E. coli associated with diarrheal disease are the ones named for their O-antigen and flagellar H-antigen, such as O157:H7. There are about 30 E. coli strains with various combinations of O-H factors known to cause diarrheal disease in people.
The E. coli Shiga toxin (though not the bacterium itself) can pass through the epithelial cell layer to become systemic, and eventually the toxin will accumulate in the kidneys. This can lead to patients experiencing hemolytic uremic syndrome (HUS) and kidney failure, leading to lifelong dialysis or need for a transplant. An immune response that prevents the E. coli from attaching will prevent the bacterium from secreting toxin in close proximity to the epithelial cells and decrease likelihood of HUS development.
Burkholderia is a bacterial genus whose member species have been weaponized in the past, and which remain potent disease-causing agents around the world.
B. mallei causes glanders, a disease mostly of horses and their handlers. It is a respiratory infection that can become systemic if not treated. B. pseudomallei causes melioidosis, a disease that can manifest in many ways. It is endemic in many tropical regions around the world, found in over 79 countries so far.
Coating gold nanoparticles with antigens against which the immune response will be protective is a method Alfredo has used for a number of candidate vaccines, including one against E. coli and one against B. pseudomallei. The nanoparticles can have the gold cleaved off to provide different functional variants of the same vaccine.
Links for this Episode:
Alfredo Torres webpage at University of Texas Medical Branch McWilliams BD and Torres AG. Enterohemorrhagic Escherichia coli Adhesins. Microbiology Spectrum . 2013. Sanchez-Villamil JI et al . Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic Escherichia coli O157:H7. mBio . 2019. Wiersinga WJ et al . Melioidosis. Nature Reviews Disease Primers . 2018. Khakhum N. et al . Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. PLOS Neglected Tropical Diseases . 2019. Torres AG. Common Sense Can Keep You Safe in E. coli Outbreak. Galveston County Daily News. 2020. ABRCMS: Annual Biomedical Research Conference for Minority Students MTM: Burkholderia pseudomallei & the neglected tropical disease melioidosis with Direk Limmathurotsakul HOM Tidbit: Kiyoshi Shiga Biography in Clinical Infectious Diseases
126: Placental biology, infection and immunity with Carolyn Coyne
2020/02/14
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Does the fetus have a microbiome? How does the placenta prevent infection? Carolyn Coyne talks about placental structure and biology, and why studying the maternal-fetal interface remains a critical area of research.
Julie’s Biggest Takeaways:
The placenta forms within 3-5 days post conception as a single layer of cells surrounding the fertilized embryo. These cells differentiate and develop into more complex structures.
Very few microbes cause fetal disease. Of those that do, the disease-causing microorganisms are diverse and can lead to serious congenital defects or even death of a developing fetus. These microbes are largely grouped into the TORCH (now TORCH-Z) microorganisms:
Toxoplasma gondii Other (a variety of different bacteria and viruses) Rubella Cytomegalovirus Herpesviruses Zika virus
The fetus is immunologically immature and unable to protect itself. Some of the maternal immunological molecules (such as maternal antibodies) cross the placenta to protect the fetus, but that only happens during later stages of fetal development. Between the first and second trimesters, the maternal vasculature reorganizes and maternal antibodies can begin to reach the fetus. This increases over time, until the end of the third trimester, when there is a higher concentration of maternal antibodies in fetal blood than in maternal blood.
In the later stages of development, the placenta is coated in a layer of fused cells, leading to a shared cytoplasm that covers the entire surface area of the placenta. This fused-cell layer is formed from syncytiotrophoblasts, and the fusion is facilitated by the activity of an endogenous retrovirus fusion protein.
Syncytiotrophoblasts are extremely resistant to infection with a number of different pathogens, and pathogen types. In initial tests experiments, Carolyn and her research team discovered that these cells releasing certain antimicrobial molecules to share protective properties. Syncytiotrophoblasts secrete type III interferons, which play a big role at barrier surfaces such as the airway and the gut—but unlike these barriers, the syncytiotrophoblast cells secrete type III interferons constitutively.
Links for this Episode:
Carolyn Coyne Website on the University of Pittsburgh School of Medicine Arora N. et al . Microbial Vertical Transmission during Human Pregnancy. Cell Host & Microbe . May 2017. Coyne C.B. The Tree(s) of Life: The Human Placenta and My Journey to Learn More About It. PLoS Pathogens . April 2016. Ander S.E. et al . Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines. mBio . January 2018. Wells A.I. and Coyne C.B. Type III Interferons in Antiviral Defenses at Barrier Surfaces. Trends in Immunology . October 2018. Ander S.E. Diamond M.S. and Coyne C.B. Immune Responses at the Materna-Fetal Interface. Science Immunology . January 2019. HOM Tidbit: Women in Microbiology HOM Tidbit: Small Things Considered blog post: Retroviruses, the Placenta, and the Genomic Junk Drawer
125: Coronavirus Antiviral Drug Discovery with Timothy Sheahan
2020/01/31
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Are there drugs that can treat coronaviruses? Timothy Sheahan talks about his drug discovery work on a compound that can inhibit all coronaviruses tested so far, and tells how his career path took him to pharmaceutical antiviral research and then back to academia.
Julie’s Biggest Takeaways:
Even though the MERS-CoV was discovered as a human pathogen in 2012, it was likely percolating as a disease agent for a long time before that. Banked camel serum provides evidence that the virus had been circulating in camels for several decades prior.
Differentiated ex vivo lung cultures allow study of virus infection in a 3D model representation for studying viral infection, including target cell types of both MERS-CoV and SARS-CoV.
SARS-CoV prefers ciliated epithelial cells Ace2 MERS-CoV prefers nonciliated epithelial cells DPP4
Coronavirus disease in people takes place over a course of about 2 weeks. In mice, the disease is similar, but progression is faster, taking about 1 week.
The drug remdesivir (RDV) is a nucleoside analog that inhibits the coronavirus RNA-dependent RNA polymerase (RDRP). Remdesivir activity has not been tested against nCoV2019, but similarity to other viruses is promising. Bioinformatic approaches show that the nCoV2019 RDRP is 99% similar and 96% identical to SARS-CoV RDRP. Remdesivir works against every coronavirus tested so far, including viruses with highly divergent RDRP sequences, so remdesivir is likely to be effective again nCoV2019. Experiments must still be performed before reaching this conclusion, of course.
Tim also hopes to discover the genetic determinants that will allow a chronic hepatitis C virus (HCV) infection in mice, but not standard inbred mice. He uses outbred mice meant to mimic the diversity of the human population, and strengthen the results. Understanding these determinants would inform human studies to better understand chronic HCV infection.
Links for this Episode:
MTM Listener Survey , only takes 3 minutes. Thanks!
TWiV 584: Year of the Coronavirus
Timothy Sheahan website at University of North Carolina Sheahan T.P. et al . Broad-Spectrum Antiviral GS-5734 Inhibits both Epidemic and Zoonotic Coronaviruses. Science Tranlational Medicine . 2017. Sheahan T.P. et al . Comparative Therapeutic Efficacy of Remdesivir and Combination Lopinavir, Ritonavir, and Interferon Beta against MERS-CoV. Nature Communications . 2020. Agostini M.L. et al . Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio . 2018. ASM Coronavirus Resource Page HOM Tidbit: Baltimore D. In Vitro Synthesis of Viral RNA by the Poliovirus RNA Polymerase. PNAS . 1964.
124: Gastroenteritis Viruses with Mary Estes
2020/01/10
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Viral gastroenteritis around the world causes 200,000 deaths globally each year. Mary Estes talks about her work on 2 gastroenteritis-causing viruses, rotavirus and norovirus, and tells the story of her discovery of the first viral enterotoxin. She also describes how noroviruses have changed from human volunteer studies to studies using “miniguts,” a system now used with many enteropathogenic microorganisms.
Julie’s Biggest Takeaways:
Rotaviruses and noroviruses kill 200,000 people annually, despite an available rotavirus vaccine and current anti-infective measures. Rotavirus is generally associated with gastrointestinal disease in the very young and the very old, while norovirus infects people at all life stages.
Rotavirus is so stable that even when viral samples are extremely dessicated by lyophilization, the samples remain perfectly infectious. Rotavirus stability is largely due to 3 concentric capsid cells.
NSP4 is a rotavirus enterotoxin, and the first viral enterotoxin to be discovered. It affects the concentration of the intracellular calcium pools. By activating the calcium chloride channel, NSP4 forces chloride and water to be excreted, directly leading to diarrhea. NSP4 is secreted from infected cells and can also disrupt calcium concentrations of neighboring cells, amplifying the effect of a single infected cell.
Rotarix® and RotaTeq® are 2 different attenuated rotavirus vaccines. One contains a single attenuated viral strain while the other contains 5 attenuated viral strains; both vaccines have high efficacy in developed countries and slightly lower efficacy in developing countries. Why vaccine efficacy is lower in developing countries is uncertain, with many hypotheses including microbiome-based effects under study now.
Human enteroids, or “miniguts,” offer insight into complex virus-cell interactions. These stem-cell derived miniguts can be generated from different types of animal stem cells, and the enteroids they become reflect the same host-barrier restriction as the animal of origin. The miniguts can be used to culture many sorts of viruses and other microorganisms, such as bacteria and protozoa.
Links for this Episode:
Mary Estes Website at Baylor College of Medicine Hyser J.M. et al . Rotavirus Disrupts Calcium Homeostasis by NSP4 Viroporin Activity. mBio . 2010. Crawford S.E. et al . COPII Vesicle Transport is Required for Rotavirus NSP4 Interaction with the Autophagy Protein LC3 II and Trafficking to Viroplasms. J Virology. 2019. Ettayebi K. et al . Replication of Human Noroviruses in Stem Cell-Derived Human Enteroids. Science . 2016. In J.G. et al . Human Mini-Guts: New Insignts into Intestinal Physiology and Host-Pathogen Interactions. Nat Rev Gastroenterol Hepatol. 2016. Finkbeiner S.R. et al . Stem Cell-Derived Human Intestinal Organoids as an Infection Model for Rotaviruses. mBio . 2012. Henning S.J. and Estes M.K. Women in Science: Hints for Success. Gastroenterology . 2015. Kapikian A.Z. et al . Visualization of a 27-nm Particle Associated with Acute Infectious Nonbacterial Gastroenteritis. Journal of Virology . 1972. HOM Tidbit: Smith K.N. The Iron Long was just an Engineer’s Side Project. Forbes . 2019. HOM Tidbit: Ramirez M. Living Inside a Canister: Dallas Polio Survivor is One of Few People Left in U.S. Using Iron Lung. Dallas Morning Star . 2018.
123: SAR11 and Other Marine Microbes with Steve Giovannoni
2019/12/21
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The most abundant organism on Earth lives in its seas: the marine bacterium SAR11. Steve Giovannoni describes how the origins of SAR11 provided its name, and the ways that studying SAR11 have taught scientists about ocean ecology. He also discusses how the different depths of the ocean vary in their microbial compositions and what his big questions are in marine microbiology.
Different depths of the ocean have different habitats, but the microbes vary continuously, based in part on light availability:
Surface light facilitates photosynthesis by algal cells. These primary producers fix carbon for the entire ecosystem! Because nutrients are readily available, the cell concentration in surface waters can reach nearly 1,000,000 cells/ml. The twilight zone offers dim light. Microbes in this area mainly use carbon sources generated by the surface-dwelling microbes. Below a few hundred meters, cell concentrations drop to 10,000-100,000 cells/ml. The deep ocean has no light and the microbes that live here have significantly different biochemistries and metabolisms.
SAR11 is small in both physical size and genome size (0.37–0.89 µm and 1.3 million base pairs, respectively). It is nevertheless the most abundant organism on the planet, with more than 1028 cells estimated to exist worldwide. These cells convert between 6-37% of the carbon fixed in the oceans daily. SAR11 in different niches have ecotypes with different specialties but look physically similar and have very similar genome sequences.
Naturally, the most abundant cells in the ocean have the most abundant parasites: bacteriophages called pelagiphages infect SAR11 all over the world. SAR11 and pelagiphages are under constant evolution, though there doesn’t seem to be a CRISPR system in the Pelagibacter genome; these bacteria largely use other mechanisms to evade phage infection.
SAR11 is like a house with the lights on all the time, in that the cells constitutively express most metabolic genes. For example, SAR11 metabolizes dimethylsulfoniopropionate (DMSP) into dimethyl sulfide (DMS) and methanethiol (MeSH), which can be produced as soon as the cells are exposed to DMSP. While this may seem energetically expensive, the cells must capitalize on their encounters with this transient resource, often found only at low concentrations, and this capitalization requires the investment of protein production. The cost of metabolic gene regulation outweighs the benefits in this particular case.
SAR11 and SAR202 are the poles on the spectrum of heterotrophic marine bacteria. SAR11 is very efficient at accessing and using the organic compounds that come from the phytoplankton (also called the labile organic matter). SAR202, found in the deeper part of the ocean, specializes in hard-to-access carbon compounds that other bacteria can’t access.
Links for This Episode
MTM Listener Survey , only takes 3 minutes. Thanks! Stephen Giovannoni website at Oregon State University OSU High Throughput Microbial Cultivation Lab Carini P. et al. Discovery of SAR11 Growth Requirement for Thiamin’s Pyrimidine Precursor and its Distribution in the Sargasso Sea . ISME J. 2014. Sun J. et al. The Abundant Marine Bacterium Pelagibacter Simultaneously Catabolizes Dimethylsulfoniopropionate to the Gases Dimethyl Sulfide and Methanethiol. Nature Microbiology. 2016. Moore E.R. et al. Pelagibacter Metabolism of Diatom-Derived Volatile Organic Compounds Imposes an Energetic Tax on Photosynthetic Carbon Fixation. Environmental Microbiology. 2019. HOM Tidbit: Sagan L. On the Origin of Mitosing Cells. 1967. HOM Tidbit: Cellmates (Radiolab podcast episode) ASM Article: The Origin of Eukaryotes: Where Science and Pop Culture Collide
122: Prions and Chronic Wasting Disease with Jason Bartz
2019/12/06
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Can a protein be contagious? Jason Bartz discusses his work on prion proteins, which cause spongiform encephalopathy and can be transmitted by ingestion or inhalation among some animals. He further discusses how prions can exist as different strains, and what techniques may help improve diagnosis of subclinical infections.
Links for this Episode:
Jason Bartz Creighton University website
Holec SAM, Yuan Q, and Bartz JC. Alteration of Prion Strain Emergence by Nonhost Factors. mSphere . 2019.
Yuan Q et al . Dehydration of Prions on Environmentally Relevant Surfaces Protects Them from Inactivation by Freezing and Thawing. Journal of Virology . 2018.
Bartz JC. Prion Strain Diversity. Cold Spring Harbor Perspectives in Medicine . 2016.
Bartz JC. From Slow Viruses to Prions PLoS Pathogens . 2016.
Deleault NR, Harris BT, Rees JR, Supattapone S. Formation of native prions from minimal components in vitro. Proceedings of the National Academy of Sciences. 2007.
Planet Money Episode 952: Sperm Banks
121: Microbial Interkingdom Interactions with Deb Hogan
2019/11/21
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Microbial interactions drive microbial evolution, and in a polymicrobial infection, these interactions can determine patient outcome. Deb Hogan talks about her research on interkingdom interactions between the bacterium Pseudomonas and the fungus Candida , 2 organisms that can cause serious illness in cystic fibrosis patients’ lung infections. Her research aims to better characterize these interactions and to develop better diagnostic tools for assessing disease progression and treatment.
Links for this Episode:
Deb Hogan Lab Website
Demers EG et al . Evolution of Drug Resistance in an Antifungal-Naive Chronic Candida lusitaniae Infection. PNAS. 2018.
Lewis KA et al . Ethanol Decreases Pseudomonas aeruginosa Flagella Motility through the Regulation of Flagellar Stators. Journal of Bacteriology . 2019.
Gifford AH et al . Use of a Multiplex Transcript Method for Analysis of Pseudomonas aeruginosa Gene Expression Profiles in the Cystic Fibrosis Lung. Infection and Immunity . 2016.
Grahl N et al . Profiling of Bacterial and Fungal Microbial Communities in Cystic Fibrosis Sputum Using RNA. mSphere . 2018.
Microbiology Resource of the Month: The Aeminium ludgeri Genome Sequence
HOM Tidbit: https://www.sciencedirect.com/science/article/pii/S0065216408705628
HOM Tidbit: The Frozen Potential of Microbial Collections
Bonus: Diagnosing C. diff Infections for Optimal Patient Outcomes with Colleen Kraft
2019/11/18
Why is C. diff such a serious disease and what are clinical microbiologists doing to improve patient outcomes with better diagnostic tools?
120: Antibiotic-Resistant Infections in Hospital Sinks with Amy Mathers
2019/11/08
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Many hospital-acquired bacterial infections are also drug-resistant. Amy Mathers describes her work tracking these bacteria to their reservoir in hospital sinks, and what tools allowed her team to make these discoveries. Mathers also discusses her work on Klebsiella , a bacterial pathogen for the modern era.
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Julie’s Biggest Takeaways
Nosocomial infections are a type of opportunistic infection: one that wouldn’t normally cause disease in healthy individuals. Once the immune system is compromised due to other infection or treatment, the opportunist bacteria take advantage of the conditions to grow to higher numbers and cause disease.
How are different pathogens transmitted in the hospital? Previously, transmission was considered to occur from one patient to a second patient, perhaps via a healthcare worker. When patients from very different parts of the hospital began to come down with the same resistant strain of bacteria, without interacting through the same space or staff, researchers began to look at a different reservoir: the hospital wastewater.
How does the bacteria get from the sink to the patients? The bacteria, existing in a biofilm in the pipe right below the drain, can be transferred in droplets when the water is run. These droplets can fall as far as 36 inches from the drain plate and can contaminate the sink bowl or patient care items next to the sink.
Some of the solutions to decrease bacterial dispersion from hospital sinks are very simple: for example, offsetting the drain from the tap, which keeps the water from directly running onto the drain, helps decrease the force with which the water hits the drain and therefore decreases bacterial dispersion.
The Sink Lab at University of Virginia couldn’t replicate the bacterial growth patterns seen in the rest of the building; in particular, there were fewer protein nutrients that promoted bacterial growth. By setting up a camera observation of sink stations used in the hospital, the team realized that the waste thrown down the sink (extra soda, milk, soup, etc) was feeding the microbial biofilm. This helps the CRE in the biofilms in the sinks thrive.
Links for This Episode MTM Listener Survey , only takes 3 minutes. Thanks! Amy Mathers website at University of Virginia The Sink Lab at UVA Kotay SM et al. Droplet- Rather than Aerosol-Mediated Dispersion is the Primary Mechanism of Bacterial Transmission from Contaminated Hand-Washing Sink Traps. Applied and Environmental Microbiology. 2018. Mather AJ et al. Klebsiella quasipneumoniae Provides a Windo into Carbapenemase Gene Transfer, Plasmid Rearrangements, and Patient Interactions within the Hospital Environment. Antimicrobial Agents and Chemotherapy. 2018. Kotay S et al. Spread from the Sink to the Patient: in situ Study Using Green Fluorescent Protein (GFP)-Expressing Escherichia coli to Model Bacteral Dispersion from Hand-Washuing Sink-Trap Reservoirs. Applied and Environmental Microbiology. 2016.
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
119: Microbiome Diversity and Structural Variation with Ami Bhatt
2019/10/24
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How do medical professionals incorporate microbiome science into their patient care? Ami Bhatt discusses her research on the diversity within and between human gut microbiomes, and how this research is slowly and carefully being used to build new patient care recommendations.
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Julie’s Biggest Takeaways
Although these terms are often used interchangeably, microbiome and microbiota represent distinct samples types:
Microbiota represents all the organisms that live within a community: archaea, bacteria, viruses, and fungi. Microbiome is the genomes or transcriptomes of these organisms.
The gut microbiota may often be referred to as a single entity, but the gastrointestinal tract has many different niches. Alterations in pH, cell type, and the available nutrients provide different selective pressures for the microorganisms that reside in these conditions.
By clustering small proteins based on similarity, Ami’s group was able to identify over 4000 new families of small proteins from existing microbiome datasets. Some of these were found among all microbiome datasets while others were found only in human microbiomes, which provides a clue to their potential housekeeping versus host-microbe-interaction functionality, although the exact functions are still unknown.
Outcomes for non-infectious diseases are affected by the gut microbiome. Ami and her colleagues have worked with transplant patients to understand what type of diversity and which strains play a role in best outcome for cancer therapy patients, such as patients receiving bone marrow transplants. Medical doctors are beginning to incorporate new patient care in light of new microbiome studies.
Understanding the effects of the gut microbiome on human health have helped slowly change patient care in some settings. For example, doctors are reconsidering recommendations for immunocompromised people to stay away from fresh fruits and vegetables, a recommendation previously made due to the potential risk of patients exposure to pathogenic microbes. The benefit of a wide variety of fiber sources, which promote a diverse and robust microbiome, may turn out to outweigh this risk.
Links for This Episode MTM Listener Survey , only takes 3 minutes. Thanks! Ami Bhatt lab website Brewster R. et al. Surveying Gut Microbiome Research in Africans: Toward Improved Diversity and Representation. Trends in Microbiology. Oct 1 2019. Sberro H. et al. Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes. Cell August 22 2019. Andermann T. et al. The Microbiome and hematopoietic Cell Transplantation: Past, Present, and Future. Biol Blood Marrow Transplant. July 1 2019. Bloomberg: Superbugs Deadlier Than Cancer Put Chemotherapy into Question Clinical Guide to Probiotic Products Available in USA HOM Tidbit: Rous P. A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells. Journal of Experimental Medicine. April 1 1911. ASM Article: A Brief History of Cancer Virology
118: Lyme Disease and Other Tick-Borne Infections with Jorge Benach
2019/10/11
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Identified in the 1980s, Borrelia burgdorferi and other Lyme disease-associated spirochetes have since been found throughout the world. Jorge Benach answers questions about Lyme Disease symptoms, his role in identifying the causative bacterium, and his current research on multispecies pathogens carried by hard-bodied ticks.
Julie’s Biggest Takeaways
Erythema migrans (the classic bullseye rash) is the most common manifestation that drives people to go see the doctor to be diagnosed with Lyme disease, but only about 40% of people diagnosed with Lyme disease experience erythema migrans.
Lyme disease can progress to serious secondary manifestations. Why some patients experience these additional disease manifestations, but others do not, is one of the heaviest areas of study in Lyme disease.
Though Borrelia doesn’t have virulence factors that mediate tissue damage, it does avoid the immune system via antigenic variation. When the bacterium is first introduced into a new human host, that person’s immune system generates reactions to the outer membrane components. These bacterial components change over time, leaving the immune response lagging behind and unable to clear the infection.
Ixodes ticks are the vector for Lyme disease and there are 3 stages in the Ixodes tick life:
Larvae : the stage during which the tick is most likely to become infected by feeding on a rodent. Nymph : the stage most likely to infect a person (due to their small size, they are less likely to draw attention while feeding). Adult : the stage when the tick develops into a sexual adult; females are most likely to be infected but because female ticks are large, most people will detect and pull out a feeding adult. Ticks feed for 2-4 days; removing a tick in the first 48 hours of attachment decreases the chance for transmission to the patient.
Long Island is seeing anecdotal increases of Amblioma ticks (the Lone Star tick), which can transmit the human pathogen Ehrlichia . These anecdotal increases were one of the motivations behind a recently published survey of ticks and the human pathogens they carry.
Links for This Episode MTM Listener Survey , it only takes 3 minutes. Thanks! Jorge Benach website at Renaissance School of Medicine Stony Brook University Sanchez-Vicente S. et al. Polymicrobial Nature of Tick-Borne Diseases . mBio. September 10 2019. Monzón J.D. et al. Populaiton and Evolutionary Genomics of Amblyomma americanum, and Expanding Arthropod Disease Vector. Genome Biol Evol. May 2016. ASM Article: The Bulls-Eye Rash of Lyme Disease: Investigating the Cutaneous Host-Pathogen Dynamics of Erythema Migrans Patient Zero podcast
HOM Tidbit: Barbour A.G. and Benach J.L. Discovery of the Lyme Disease Agent. mBio. September 17 2019.
117: Influenza Virus Evolution with Jesse Bloom
2019/09/26
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Influenza is famous for its ability to mutate and evolve but are mutations always the virus’ friend? Jesse Bloom discusses his work on influenza escape from serum through mutation and how mutations affect influenza virus function and transmission.
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Julie’s Biggest Takeaways
Influenza is famous for its ability to mutate and evolve through two major mechanisms:
Antigenic drift occurs when a few mutations accumulate in the influenza genome and lead to seasonal changes. Antigenic shift occurs when two influenza strains recombine their genomes to form one previously unknown in human populations.
Avian influenza has caused thousands of zoonotic cases, in which the virus is transmitted from birds to people. This causes serious disease but the virus doesn’t easily pass from person-to-person, limiting how many people are affected. When a zoonotic case becomes easily transmissible between people, as is suspected occurred in the 1918 influenza pandemic, the outcome can be very serious for many, many people.
During antigenic drift, the virus accumulates mutations randomly throughout its genome. Mutations in the hemagglutinin (HA) glycoprotein gene are the mutations most likely to affect the ability of antibodies to attach and block HA during viral infection of a new host cell. The circulating human H3N2 influenza A virus accumulates approximately 3-4 mutations annually within its HA gene, representing a 0.5-1% change. On average, it takes 5-7 years of these mutations accumulating until a viral strain can reinfect a previously infected person.
The changes in the influenza sequence are responsible for waning immunity against the annually circulating strain. This was demonstrated when a flu strain from the 1950s was inadvertently reintroduced in the 1970s; older people who had previously been infected were protected against this exact same strain.
Influenza viruses can escape from sera, which contains many different antibodies, similar to how they can escape from a single monoclonal antibody: through mutations in major antibody binding sites. However, the mutations that allow escape from one person’s serum are different from the mutations that allow escape from another person’s serum. This means the strains that escape one person’s immune system may only be able to infect those with similar immunity.
Links for This Episode MTM Listener Survey , only takes 3 minutes. Thanks! Jesse Bloom’s lab website Guns Germs and Steel by Jared Diamond Lee J.M. et al. Mapping Person-to-Person Variation in Viral Mutations that Escape Polyclonal Serum Targeting Influenza Hemagglutinin. eLife. August 2019. Xue K.S. et al. Cooperating H3N2 Influenza Virus Variants are not Detectable in Primary Clinical Samples. mSphere. January 2018. Francis Arnold at ASM Microbe: Innovation by Evolution: Bringing New Chemistry to Life
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan .
116: Citrus Greening and the Microbiome in Diabetes with Graciela Lorca
2019/09/13
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Graciela Lorca studies genetic systems to find positive and negative microbial interactions that lead to disease. She talks about her discovery of chemical inhibitors for the citrus greening disease bacterium, Liberibacter asiaticus, and how a specific strain of Lactobacillus johnsonii modulates the immune system and may help prevent development of diabetes in people.
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Julie’s Biggest Takeaways
Citrus greening disease, or huanglongbing, is a disease of citrus trees causing a major epidemic among citrus farmers around the world. The disease causes trees to sicken and eventually die, and is best diagnosed by PCR amplification of the bacterial DNA from the bacterium that causes the disease, Liberibacter asiaticus . Because the disease spreads through the tree at different rates, it’s important that many samples be tested for accurate diagnosis.
Quarantining the disease has proved difficult, as undiagnosed roots can transmit the disease if they are used to hybridize with canopy plants. The disease becomes even harder to contain under bad weather conditions: the high winds of recent hurricanes can scatter the insect vector, the Asian citrus psyllid, leading to infection of new orchards.
Although L. asiaticus can’t be cultured, Graciela performed a screen on L. asiaticus transcription factors that were produced by E. coli . These were tested for inhibition by a chemical library, and discovered that a common treatment for gout, benzbromarone, inhibited protein activity. This discovery was confirmed using in vivo infected plants and by expressing the gene in related bacterial species, Graciela and her team predict the protein plays a role in responding to osmotic stress. The protein target of the chemical differs widely between citrus greening disease and gout, but the protein-chemical interaction is similar enough to allow protein inhibition.
Is there a link between the microbiome and diabetes? 10 years ago, Lactobacillus johnsonii can rescue animals that are predisposed to diabetes. L. johnsonii inactivates a host enzyme, IDO, which regulates proinflammatory responses. Activated immune cells can travel to the pancreas and attack beta cells, leading to diabetes. Regulating the proinflammatory response by administering L. johnsonii as probiotics offers the opportunity to control development of diabetes in predisposed people.
Links for This Episode MTM Listener Survey , only takes 3 minutes. Thanks! Graciela Lorca’s lab website Pagliai F.A. et al. The Transcriptional Activator LdtR from ‘Candidatus Liberibacter asiaticus’ Mediates Osmotic Stress Tolerance. PLoS Pathogens. April 2014. Lai K.K., Lorca G.L. and Gonzalez C.F. Biochemical Properties of Two Cinnamoyl Esterases Purified from a Lactobacillus johnsonii Strain Isolated from Stool Samples of Diabetes-Resistant Rats. Applied and Environmental Microbiology. August 2009. Marcial G.E. et al. Lactobacillus johnsonii N6.2 Modulates the Host Immune Response: A Double-Blind, Randomized Trial in Healthy Adults. Frontiers in Immunology. June 2017. HOM Tidbit: Hartmann A., Rothballer M., and Schmid M. Lorenz Hiltner, a Pioneer in Rhisophere Microbial Ecology and Soil Bacteriology Research. Plant and Soil November 2008.
115: 20 Years of the Lab Response Network with Julie Villanueva
2019/08/30
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When a new biothreat or emerging infectious agent threatens, how are diagnostic protocols put into place? It’s up to the Laboratory Response Network (LRN), a multipartner network of public health, clinical and other labs, to generate and distribute reagents, and provide training to detect these threats. Julie Villanueva, Chief of the Laboratory Preparedness and Response Branch at the CDC, talks about the LRN and how no two weeks on the job are alike.
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Julie’s Biggest Takeaways
In the mid-1990s, the CDC joined public health representatives along with the Departments of Defense and Justice to determine the best way to prepare and respond to potential bioterrorism threats. The result was the Laboratory Response Network (LRN), founded in 1999.
The LRN provides infrastructure to detect potential pathogens. Though first put into place to detect and prevent bioterror events, the LRN has also been able to detect infectious diseases that have emerged through other means.
When a new disease emerges, there are typically no widely available tests to diagnose the disease. The CDC works hard to quickly develop diagnostic tests, validate the tests, manufacture the necessary reagents, and ship these out to the reference labs that are part of the LRN. This ensures that each lab can accurately reach the same result with the same sample.
The laboratory response network requires more than just developing and deploying diagnostic tests. The LRN must also provide
Training for LRN scientists. Proficiency testing to test the network. Reporting protocols for sending results.
What diseases keep Julie up at night? A viral hemorrhagic fever is one, and microorganisms that evolve quickly and have high pathogenic potential, like influenza virus, is another.
Featured Quotes
“Our collaborations across other federal agencies like the FDA and the USDA are really important for us to stay on the cutting edge of what could be emerging.”
“Partnerships are so critical when managing an outbreak. There’s never an outbreak that only affects one group of people...there are lots of different facets of an outbreak that need to be addressed and partnerships are critical for managing and trying to mitigate as much as possible.”
“The LRN primarily focuses on diagnostics, this is what the network really does. It’s made to be able to detect biothreats and emerging infectious diseases in both clinical and environmental samples.”
“We’re always looking at new technologies for faster, more sensitive, and more specific tests.”
“Every outbreak has been different in a different way, and I’ve learned something every time. I think that each outbreak has taught us a few things that work well within the network and a few things with which we can improve, and continued improvement is very important to us. For example, the Ebola outbreak in 2014-16 really highlighted the need for biosafety and biosecurity procedures all across not only the network but also our hospitals...we learn something different from every outbreak.”
Links for This Episode MTM Listener Survey , only takes 3 minutes. Thanks! The Laboratory Response Network (CDC website)
HOM: The Origin of In Situ Hybridization - a Personal History
114: Global Public Health with George F. Gao
2019/08/15
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George F. Gao discusses how China CDC promotes global public health during outbreaks SARS and Ebola. He also talks about running a structural biology lab, the importance of both basic and translational research, and the most important discovery of the 20th century.
Julie’s Biggest Takeaways :
China CDC was founded in 2001. Its experience with the SARS outbreak informed its response to the western Africa Ebola outbreak in 2014-2016, having learned that viruses don’t care about national borders and can quickly become an international problem. Responding to any major outbreak serves both altruistic and selfish motives, since quelling the outbreak decreases the chance that the disease will continue to circulate, potentially reaching your country.
Basic research is fundamental for many translational applications to improve human health. By measuring the mutation rate, for example, of a circulating virus, scientists can determine if previous isolates can be used to generate vaccines. The basic research that led to new nucleic acid sequencing techniques has many important applications!
When asking other scientists what the most important discovery of the 20th century is, many biomedical scientists name the discovery of the double helix. George points out that bird migration patterns have influenced our understanding of avian diseases like the flu. This discovery led scientists to understand more about the annual transmission patterns of flu, highlighting the importance of interdisciplinary research.
George has a foot in both basic and translational sciences and is an ardent supporter of both. The difficulty is in identifying basic research that has potential for application and providing opportunities to basic researchers to create companies and products based on their research. Another hurdles is collaborating and coordinating to ensure people talk to each other
George lists the 4 Cs required to promote science, public health and societal development:
Collaboration Cooperation Communication Competition
Links for this Episode :
George F. Gao Lab Website
Gao GF and Feng Y. On the Ground in Sierra Leone. Science 2014.
Carroll D et al . The Global Virome Project. Science 2018.
Watts G. George F. Gao: Head of China CDC Signals a More Global Outlook. Lancet 2018.
Forging the Path for Polio Vaccination: Isabel Morgan and Dorothy Horstmann
113: Bacteriophage Interactions in the Gut with Jeremy Barr
2019/08/03
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Bacteriophage are viruses that infect specific bacteria. Jeremy Barr discusses his discovery that phage interact with (but don’t infect) mammalian epithelial cells. He explains how these different organisms: bacteria, bacteriophage, and the mammalian host, may exist in three-way symbioses.
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Julie’s Biggest Takeaways
Jeremy’s work as a postdoc focused on developing a protocol to clean phages for use in tissue culture. He and his advisor, Forest Rohwer, were asked to use this protocol to clean phages for a patient extremely sick with a multidrug-resistant Acinetobacter baumannii isolate. Within 24 hours, they used an experimental lab method to clean and purify phages that were used in an experimental procedure to treat a very sick person; phage therapy ultimately saved his life.
Jeremy discovered that phages can pass through human epithelial cells by using a transwell system. Phage interaction with epithelial cells is not the same as an infection, since the phages cannot use mammalian molecular machinery to reproduce. Jeremy hypothesizes that the epithelial cells take up phage during active sampling from the gut, during which epithelial cells sample the environment to inform the immune system.
Jeremy’s work is building toward a model of tripartite symbioses. This includes symbiosis between bacteria and mammalian cells, between bacteria and bacteriophage, and between bacteriophage and mammalian cells. Bacteria can interact with mammalian cells to influence host cell signaling to their benefit, and Jeremy’s hypothesis is that phage will be found to do the same.
Building a gut-on-a-chip allowed Jeremy to study the interactions of phage with the gut in a controlled environment. The preliminary results suggest that the phage adapt to better adhere to the mucosal surfaces over time. Discovering the protein domains that phage use to stick to mucins opens up the possibility of using these domains in personalized therapeutics, by designing these into new phage or other therapeutics.
Jeremy’s 2 major pieces of advice for early career scientists:
Follow what excites you! Find an aspect of biology that you're really passionate about and follow that. Find amazing mentors. Contact even people you don’t directly work with, reach out to them and build your network. Links for This Episode MTM Listener Survey , only takes 3 minutes. Thanks! Jeremy Barr lab website The Perfect Predator by Steffanie Strathdee Gordillo Altamirano FL and Barr JJ. Phage Therapy in the Postantibiotic Era. Clin Microbiol Rev 2019. Nguyen S. et al. Bacteriophage Transcytosis Provides a Mechanism to Cross Epithelial Cell Layers. mBio 2017. Microbe information
112: A Career in Salmonella with Stanley Maloy
2019/07/19
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Stanley Maloy discusses his career in Salmonella research, which started with developing molecular tools and is now focused on the role of Salmonella genome plasticity in niche development. He further talks about his role in science entrepreneurship, science education, and working with an international research community.
Julie’s Biggest Takeaways :
Stanley’s career began when transposon mutagenesis was a new, cutting-edge technique, and he found the best way to learn how to apply a new method was to jump in and try it.
Antibiotic resistance has been a problem throughout Stanley’s career. The future may hold new antimicrobials that aren’t necessarily categorized as classical ‘antibiotics,’ but may offer precision therapy against specific infectious agents. Whatever the future holds, it won’t be a single answer: Stanley sees many innovations necessary to deal with the future of antibiotic-resistant infections.
Stanley’s current research is in Salmonella genome plasticity and how genomic traits influence the bacterial niche. Where do traits like exotoxins or antibiotic resistance exist in the environment, and how are they transferred to new species to influence disease? Cases of Typhoid Fever in people without known exposure to another diseased person suggest there may be an environmental reservoir. What might it be?
Stanley is a big proponent of scientist entrepreneurs and participates with the NSF Innovation Corps to promote early science start ups. In addition to creativity and the scientific process, one characteristic he encourages all entrepreneurs to develop is a good team spirit. Working collaboratively as a team is a very strong sign of success.
Stanley believes in the importance of an international science communities, and he practices what he preaches: he works closely with the scientific community of Chile. He began in 1990 by teaching an intensive lab course about techniques, and has developed a decades-long relationship with this community. These relationships allow a dialog, and were the reason Stanley ultimately turned his focus to Salmonella Typhi from Salmonella Typhimurium.
Links for this Episode :
MTM Listener Survey , only takes 3 minutes! Thanks;) Stanley Maloy website at San Diego State University This Week in Microbiology #95: A Microbe Lover in San Diego National Science Foundation Innovation Corps Journal of Microbiology and Biology Education Call for Submissions for a Special Issue on diversity and inclusion. HOM Tidbit: A Large Community Outbreak of Salmonellosis Caused by Intentional Contamination of Restaurant Salad Bars
111: The Cheese Microbiome with Rachel Dutton
2019/07/03
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Cheese rinds contain microbial communities that are relatively simple to study in the lab while offering insight into other, more complex microbial ecosystems. Rachel Dutton discusses her work studying these cheese microbiomes, one of the few microbial ecosystem types where almost all of the microorganisms are culturable.
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Julie’s Biggest Takeaways
The cheese microbiome makes a great study system because
The communities are relatively simple (as few as 3 different microbial species) The microbial members are almost all culturable (in stark contrast to most microbial communities)
The microbes colonize the cheese rind as a biofilm, which consists of the microbes and their secreted extracellular products. Like all biofilm communities, architecture and spatial structure are important for microbial interactions on cheese rinds, as are oxygen gradations, food access, and proximity to microbial neighbors.
Rachel and her lab performed DNA sequencing on over 150 cheese samples from 10 countries to identify the microbes present on these rinds. By comparing these sequences to those they could grow in the lab (Rachel’s lab makes “in vitro” cheese medium consisting of desiccated, autoclaved cheese), they realized almost all of the organisms identified by molecular means were present in their cultures.
Does the cheese environment influence the microbial communities or do the microbial communities influence the cheese environment? Both! The pH, temperature, added salt and temperature act as knobs or dials that allow cheese makers to fine tune the final cheese product.
Rachel was inspired to work on cheese after taking the Microbial Ecology course at Woods Hole, where the students spent a lot of time looking at the beautiful but complex interactions within microbial mats. Upon cutting open some Tomme de Savoie from a French colleague, she noted similarities between the microbial mat and the layered cheese rind
Featured Quotes
“The biofilm that colonizes the surface of the cheese has a lot to do with how the cheese ends up looking and smelling and tasting, and we actually eat this biofilm when we eat the cheese.”
“We’re able to see that of all of the things that we identified by reasonable sequence abundance, we could also find them in culture. This told us that we were able to get a lot of these microbes in culture, which is not really possible in microbial ecosystems, but is one of the really strong advantages of working in the fermented food community.”
“We’re looking at these interactions because they’re happening on cheese and we can study them in the lab but they are things that are happening broadly across ecosystems, which I think is very exciting.”
“We’ve done some work on the succession of species over time. You have these very very reproducible successions over time, even though a lot of these cheeses are not inoculated with specific species; these are species that are coming in from the environment but they’re very reproducible communities. There are some beautiful dynamics that happen and we’re starting to look at the interactions between species that may be driving some of these dynamics.”
“We have this big need for model systems. One of the things I hope is that we’ll have more people developing simple model systems for microbial ecology so we can compare results and see what the general principles are.”
Links for This Episode MTM Listener Survey , only takes 3 minutes! Thanks;) Rachel Dutton Lab Website Wolfe BE, Sutton JE, Santarelli M, and Dutton RJ. Cheese Rind Communities Provide Tractable Systems for in situ and in vitro Studies of Microbial Diversity. Cell 2014. Wolfe BE and Dutton RJ. Towards an ecosystems approach to cheese microbiology. Book chapter: Cheese and Microbes. ASM Press and Microbiology Spectrum (2014). Microbes After Hours: The Microbiology of Cheese (YouTube) Competition and Cooperation of Cheese Rind Microbes Exposed (The Scientist) Related: The Natural History of Cheese Mites HOM Tidbit: Peoria Historian Blog Post HOM Tidbit: Journal of Bacteriology Classic Spotlight: Crowd Sourcing Provided Penicillium Strains for the War Effort
110: Metagenomic Sequencing for Infectious Diseases Diagnostics with Charles Chiu
2019/06/13
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Most diagnostic tests look for a single microorganism, or at most a limited panel of microorganisms. Charles Chiu discusses his research on metagenomic sequencing as a diagnostic tool that can identify all potential pathogens in a given patient sample.
Links for this Episode:
MTM Listener Survey , only takes 3 minutes! Thanks;) Charles Chiu Profile at UCSF Chiu Lab at UCSF Validation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection The Eukaryotic Gut Virome in Hematopoietic Stem Cell Transplantation: New Clues in Enteric Graft-Versus-Host Disease HOM Tidbit: Dochez and Avery. The Elaboration of Specific Soluble Substance by Pneumococcus during Growth. Journal of Experimental Medicine 1917. HOM Tidbit: Kozel and Burnham-Marusich. Point-of-Care Testing for Infectious Diseases: Past, Present, and Future. Journal of Clinical Microbiology 2017.
109: Antimicrobial-Eating Microorganisms and the Resistome with Gautam Dantas
2019/05/31
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While searching for lignin-degrading soil microbes, Gautam Dantas discovered growth in an antimicrobial compound-containing control! He has since studied the resistance determinants (resistome) of soil and clinical samples to determine their similarities.
Julie’s Biggest Takeaways :
Sequencing information is extremely useful for descriptive studies, but there’s an increasing trend in microbiome studies to use the sequencing data as a basis for forming hypotheses. These hypotheses can then be tested by some variation of classical techniques, be in biochemical, culturing, animal models, etc. Surveying who is there helps scientists make testable predictions.
Gautam’s resistome research is built on the research of many, but especially inspired by:
Gerry Wright, who proposed the presence of a resistome. The resistome is a collection of genetic determinants in a microbial group that allows phenotypic resistance against antimicrobial compounds. Julian Davies, who proposed the producer hypothesis. The producer hypothesis suggests that the same microorganisms that produce antimicrobials must also be the source of resistance, because they need to be able to protect themselves against the action of their own compounds.
Gautam’s discovery of antibiotic-eating microbes was completely serendipitous! As a postdoc, he was looking for lignin-degrading soil microbes and set up a culture with antibiotics as a negative control. To his surprise, there were some soil microbes that were able to grow - using the drugs as food! Samples from 3 different states were all able to support microbial life.
The resistome of soil is very similar to the resistome of clinical samples, but the study design doesn’t allow Gautam to conclude directionality: do the genes move from the clinic to the environment or from the environment to the clinic? This requires studying the resistomes over time, rather than the snapshot analyses this study generated. However, Gautam’s group has received funding to do longitudinal studies, which will help scientists understand how resistance originates and then moves to new microbial communities.
Context is very important for determining disease. A microbe may make one person but not another sick. Context can also be the genes carried by the microbe, and E. coli is a great example of this. Some E. coli are very good at causing UTIs but cause no disease when carried in the gut.
Links for this Episode :
Take the MTM listener survey (~3 min.) Gautam Dantas lab website Wright G.D. The Antibiotic Resistome. Expert Opinion in Drug Discovery . 2010. Davies J. and Davies D. Origins and Evolution of Antibiotic Resistance. MMBR . 2010. Bloomberg: Germ-Killing Brands Now Want to Sell You Germs HOM Tidbit: Recycling Metchnikoff: Probiotics, the Intestinal Microbiome and the Quest for Long Life
108: Microbes, Heme, and Impossible Burgers with Pat Brown
2019/05/16
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Pat Brown founded Impossible Foods with a mission to replace animals as a food production technology. Here, he discusses the ways microbial engineering helps produce the plant hemoglobin that provides the Impossible Burger’s meaty qualities.
Links for this episode:
Take the MTM listener survey (~3 min.) The Microbial Reasons Why the Impossible Tastes So Good Impossible Foods The Conversation: What Makes the Impossible Burger Look and Taste Like Real Beef? Wired: The Impossible Burger: Inside the Strange Science of the Fake Meat that ‘Bleeds’ HOM Tidbit: Mendel’s letters to von Nägeli HOM Tidbit: The Mendel-Nägeli Letters, circa 1866-73 (Scientific American)
107: CRISPR, anti-CRISPR, and anti-anti-CRISPR systems with Joe Bondy-Denomy
2019/05/02
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CRISPR is a genome-editing tool, but what is its role in microbial biology and evolution? Joe Bondy-Denomy discusses his discovery of the first anti-CRISPR protein and the many unanswered questions surrounding CRISPR biology.
Julie’s Biggest Takeaways
CRISPR is a bacterial immune system that identifies and destroys specific nucleotide sequences. These sequences are most commonly associated with foreign DNA from bacteriophage or plasmids.
Bacterial acquisition of new CRISPR spacer sequences is fairly inefficient, and often a bacterium dies before acquiring and fending off a new phage infection. Only about 1 in a million cells emerge from a phage infection with a new spacer sequence, likely driven defective phages that act as a vaccine of sorts to provide spacer sequence material.
40% of bacteria and 85-90% of archaea have had some sort of CRISPR system detected in their genomic sequences.
Most bacteria have Type I CRISPR system. This system includes different proteins that serve unique functions: one holds onto CRISPR RNA, one helps identify complementary sequences, and one cleaves the actual nucleotide sequence. The Type II CRISPR system has a single protein, Cas9, which performs all of these functions by itself. Because of its simplicity, this Type II CRISPR system has become widespread as a DNA manipulation tool.
What are the inputs to CRISPR? How do bacterial cells turn CRISPR genes on and off? Do CRISPR systems serve any other regulatory functions? There are still a number of questions that need to be answered to understand the biological role of CRISPR systems.
Take the MTM listener survey (~3 min.) Joe Bondy-Denomy UCSF Lab Website Rauch BJ. Inhibition of CRISPR-Cas9 with Bacteriophage Proteins. Cell 2017. Borges AL. Bacteriophage Cooperation Suppresses CRISPR-Cas3 and Cas9 Immunity. Cell 2018. Mendoza SD. A Nucleus-Like Compartment Shields Bacteriophage DNA from CRISPR-Cas and Restriction Nucleases. bioRxiv 2018. UCSF Sandler Fellows Program HOM Tidbit: Coming of Phage Celebrating the Fiftieth Anniversary of the First Phage Course
106: Creepy dreadful wonderful parasites (and a few bacteria) with Bobbi Pritt
2019/04/18
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Julie’s Biggest Takeaways :
Parasites are incredibly varied in many characteristics, including their size! Some are microscopic, while others are macroscopic and can be seen with the naked eye. Not just small macroscopic, although some worms at 35 cm can be considered quite large. Some tapeworms can reach 50 feet!
Bobbi Pritt’s blog started as an exercise to share the cases she observed while a student at the London School of Tropical Medicine. She wanted to share these cases with students back at the Mayo Clinic, but found the audience grew to include clinical parasitologists, microbiologists, and parasite-interested people worldwide. Part of its success relies on its succinctness: a short, digestible case study with the minimum information needed to make a diagnosis.
Pritt’s research focuses on developing molecular tests to detect microorganism RNA or DNA. Molecular tests can be used as a complementary diagnostic test or as the primary test, which can give healthcare workers definitive information to make therapeutic decisions much more quickly than a test that requires culturing the microorganism.
A new bacterium that causes Lyme disease, Borellia mayonii , was found because the molecular tests that detect Borellia burgdorferi are flexible enough to detect multiple species and can differentiate between the different types of organisms. It was an astute technologist working at the bench who recognized the readout was slightly different than
We did a tick drag, taking a white cloth and dragging it through vegetation. The Ixodes ticks that transmit Lyme disease will think the sheet is a host and will grab onto the sheet, allowing easy collection of a large number of ticks to test for bacterial presence.
One of the outstanding questions in parasitology is the relationship of Blastocystis (formerly known as Blastocystis hominis but may actually be several species) to human health. Blastocystis lives in the intestinal tract and may cause irritable bowel-like syndrome. Definitive evidence on whether Blastocystis causes intestinal disease has yet to be presented, and there is a lot of opportunity for research in this area.
Links for this Episode :
Take the MTM Listener survey (~3 min.) Creepy Dreadful Wonderful Parasites (Bobbi Pritt’s blog) ParasiteGal: Bobbi Pritt on Twitter Pritt B.S. et al. Identification of a Novel Pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infectious Disease . 2016. MTM Episode: Biofilms and Metagenomic Diagnostics in Clinical Infections with Robin Patel HOM Tidbit: Patrick Manson. On the Guinea Worm. British Medical Journal. Bobbi on This Week in Parasitism (TWiP)
105: HPV vaccination with Doug Lowy
2019/04/05
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How did discoveries made with bovine papillomavirus help scientists develop the human papillomavirus vaccine? Doug Lowy discusses his journey that began with basic research and led to the production of the HPV vaccine.
Julie’s Biggest Takeaways
In the early 1950s, the U.S. was a high-incidence country for cervical cancer. Through application of screens using the Pap smear, doctors have been able to catch and excise suspicious tissue, leading to a significant drop in incidence. Cervical cancer remains high-incidence in low- and middle-income countries; in high-incidence countries, cervical cancer is the most common form of HPV-associated cancer. In the U.S., cervical cancer represents around 50% of the HPV-associated cancers, with others like penile, anal, and oropharyngeal cancers also represented.
Henrietta Lacks, the woman from whom HeLa cells were derived, had a cervical adenocarcenoma caused by HPV-16. The viral DNA had integrated near the myc oncogene to generate high expression of this oncogene. The cell lines have been growing for decades but the epigenetic changes from HPV infection have led to a dependence of the cells on E6 and E7; if they are blocked or removed, the HeLa cells undergo apoptosis.
Lowy’s work on bovine papilloma virus (BPV) played a key role in development of the HPV vaccine. Other researchers attempting to generate a neutralizing response to the HPV capsid failed, but Lowy and his colleague Reinhard Kirnbauer had successfully achieved neutralization using BPV. By comparing HPV and BPV sequences, Lowy realized there was a single amino acid change in the HPV-16 strain that was being used as a lab standard strain; fixing this restored capsid self-assembly, led to immunogenicity and provided the basis for the HPV vaccine.
HPV L1 capsid protein has a repeating structure that induces a very high level of immune protection. Protection is so high that it is sterilizing, meaning that exposed individuals prevent any infection, not just disease. This may serve as the basis for a new strategy, using repeating structures such as ferretin in vaccine development.
The incubation between infection and development of cancer can take decades, and the vaccine has not been on the market long enough to assess a difference in cancer incidence. It has resulted in a decrease in cervical dysplasia, the endpoints used in cervical cancer screening via pap smear, but no cancer reduction has been observed yet.
Links for this Episode :
Harold zur Hausen Nobel Prize for association between HPV and cancer Lowy D. HPV Vaccination to Prevent Cervical Cancer and Other HPV-Associated Disease: From Basic Science to Effective Interventions. Journal of Clinical Investigation. Jan 2016. Schiller J. and Lowy D. Explanations for the High Potency of HPV Prophylactic Vaccines. Vaccine . August 6 2018. VAERS Vaccine Adverse Event Reporting System ASM Article: A Brief History of Cancer Virology JHU Press: Vaccines Did Not Cause Rachel’s Autism
104: Burkholderia pseudomallei and the Neglected Tropical Disease Melioidosis with Direk Limmathurotsakul
2019/03/21
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Burkholderia pseudomallei is an endemic soil-dwelling bacterium in southeast Asia, where it causes melioidosis. Direk Limmathurotsakul discusses his work to improve the official reporting numbers and how
Julie’s Biggest Takeaways:
Melioidosis can present in a number of ways, such as sepsis, pneumonia, or abscesses. Because the symptoms are not specific, diagnosis requires isolation of the Burkholderia pseudomallei bacterium. Risk factors for disease include diabetes and exposure to the soil and water in which the bacterium lives.
In 2012, only 4 people were officially reported to have died of melioidosis in Thailand, but microbiological records suggest the real number was closer to 696. Scientists like Direk worked with the government to improve reporting requirements and the numbers now reflect a more accurate assessment of the disease burden. More accurate official reporting can lead to more public health campaigns, resources, and support for both scientists and patients.
Social media campaigns and a YouTube competition help to raise local awareness of melioidosis. The YouTube competition engages the community by allowing them to enter videos in their own dialect, which then inform others about how to minimize risk factors for melioidosis.
The AMR Dictionary gives simple definitions to jargon surrounding the problem of antimicrobial resistance. The definitions are translated into multiple languages in ways that make sense with colloquialisms. For example, in Thai, many people refer to antibiotics as antiseptics or anti-inflammatory drugs, and the dictionary takes local use into consideration in its definitions.
Links for this Episode:
MTM Listener Survey
Limmathurotsakul website at MORU Tropical Health Network
Melioidosis.info
Melioidosis: the Most Neglected Tropical Disease
Antibiotic Footprint
AMR Dictionary
103: Predicting Spillover Events with Barbara Han
2019/03/08
When will the next disease outbreak occur? Why are some pests better at spreading disease than others? Disease Ecologist Barbara Han talks about her research that addresses these questions with computer modeling, as well as how modeling predictions can inform field and bench research.
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Visit asm.org/mtm for all links and notes.
102: HIV vaccines with Dan Barouch
2019/02/21
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Why have scientists struggled to generate a protective HIV vaccine? Dan Barouch lays out the unique challenges and discusses the ongoing clinical trial with an adenovirus-based vaccine developed in his lab.
Julie’s Biggest Takeaways
HIV poses unique and unprecedented challenges for vaccine development including:
Viral diversity: extremely wide range of viral diversity. No natural precedent: No human has cleared HIV based on their immune responses. Unknown correlates of protection: scientists are unsure what immune responses are important to induce.
Barouch’s group uses a vaccine strategy comprised of computationally optimized mosaic HIV Env proteins, which represent pieces of the outermost glycoprotein, Env, that have been tied together in a way expected to generate protective immunity. Early data from animal and human trials suggests these mosaic antigens generate an immune response to a wider array of HIV types than previous vaccines. Clinical trials are ongoing to see if a strategy of mosaic antigen vaccination, followed by a boost with Env protein, is protective in people.
Attenuated HIV hasn’t been used as a vaccine strategy because of fears it could revert to a disease-causing form; similar fears have prevented a whole-killed virus platform for vaccine development.
A clinical trial testing safety in 3 locations around the world demonstrated that this vaccine strategy in people elicited immune responses shown to be protective in animals. An efficacy trial is ongoing in sub-Saharan Africa, with results expected in 2021. The trial is double blinded: neither the doctor nor the patient know who was administered the candidate vaccine or who was administered the placebo.
HIV latent infection causes complications in vaccine development because
HIV latency is seeded early, possibly in the first few days of infection. Once latency is established, the individual is infected for life.
Any low level of HIV infection in vaccinated people could potentially seed this latent infection. Quickly-seeded latency means immune responses must react extremely quickly.
Featured Quotes
“The challenges in the development of a prophylactic HIV vaccine are among the toughest challenges in biomedical and scientific research.”
“HIV poses unique challenges for vaccine development and truly unprecedented challenges that have never been posed before by vaccination. One such challenge is the viral diversity: HIV exists not as a single sequence, but as numerous different viral sequences — not only throughout the world, but also throughout regions, communities, and even within the same individual. So to create a vaccine against HIV, the immune responses have to be relevant for a vast diversity of viral sequences.”
“At what efficacy level would an HIV vaccine be licenced by both the industry partners as well as the government regulators in a particular country, and at what level of efficacy would it actually have a major public health impact? It’s a moving target over time; it really depends on what the current state of the epidemic is at the time the vaccine is ready to be licensed.”
“It’s critical to have high-quality research part of the clinical efficacy trials so that success or failure or something in between, that the HIV research field learns from it, and learns what worked well and what didn’t work well, and how to make better vaccines moving forward.”
“I always encourage young scientists to pursue their dreams and to tackle hard problems. There’s a lot of easy problems to solve but some of the hardest problems are the most impactful in the end.”
Links for This Episode
MTM Listener Survey Barouch lab at the Center for Virology and Vaccine Research . MTM: Mark Connors . The Lancet : Evaluation of a Mosaic HIV-1 Vaccine in a Multicentre, Randomised, Double-Blide, Placebo-Controlled, Phase 1/2 a Clinical Trial (APPROACH) and in Rhesus Monkeys. The Lancet : A Step Forward for HIV Vaccines . Journal of Virology : Similar Epitope Specificities of IgG and IgA Antibodies Elicited by Ad26 Vector Prime, Env Protein Boost Immunizations in Rhesus Monkeys. PLoS One : First-in-Human Randomized, Controlled Trial of an oral, replicating adenovirus 26 vector vaccine for HIV-1. HOM Tidbit: I am the Berlin Patient: A Personal Reflection . HOM Tidbit: Doctor who cured Berlin Patient of HIV: ‘We knew we were doing something very special’ .
101: Structural Biology Insights into Ebola Virus with Erica Ollmann Saphire
2019/02/07
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Erica Ollmann Saphire discusses her research on Ebola virus glycoprotein and the changing nature of structural biology.
The Ebola virus glycoprotein sequence can vary up to 50% between Ebola virus species, presenting a challenge to develop pan-Ebola therapeutics or vaccines. Erica Ollmann Saphire discusses her work on antibodies that neutralize all Ebola virus species and the changing nature of the structural biology toolkit used to study them.
Check out all our great podcasts at asm.org/podcast
MTM Listener Survey: asm.org/mtmpoll Ollmann-Saphire Lab Site Protein Database Isolation of Potent Neutralizing Antibodies from a Survivor of the 2014 Ebola Virus Outbreak. Science 2016. Systemic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Proteciton. Cell 2018. Structural Basis of Pan-Ebolavirus Neutralization by a Human Antibody against a Conserved, yet Cryptic Epitope. mBio 2018. Tenacious Researchers Identify a Weakness in All Ebolaviruses. mBio 2018. HOM Tidbit: How “Lassa,” a small Nigerian Town, was Stigmatized by having a Killer Virus Named after it.
100: It’s our 100th Episode! A retrospective into Meet the Microbiologist with Merry Buckley and Carl Zimmer
2019/01/25
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We pull back the curtain as former show hosts Merry Buckley and Carl Zimmer talk Meet the Scientist origins, favorite interviews and microbial topics.
Julie’s Biggest Takeaways :
Though the show started before podcasts were as popular as they are now, this didn’t pose a problem for Merry or Carl when soliciting guests - scientists were happy to have their work featured and to discuss their research.
Inviting guests may involve bringing in a mix of experienced and early-career researchers, but both Merry and Carl agreed that the science is the major deciding factor when selecting guests.
The ability to steer away from technical jargon and to use accessible, everyday analogies is one of the features shared by favorite guests. Carl uses the example of Bonnie Bassler, who explains bacterial quorum sensing as a communication mechanism.
Delving into the personal motivations and experiences of guests can be tough, even when these experiences relate to science. Merry uses Abigail Salyers’ claim of the English teacher who supported her through her high-school pregnancy and Julie uses Ilaria Capua’s experience when falsely accused of trafficking viruses for money.
Scientists can make themselves more visible to scientists and nonscientists by promoting their research on social media, particularly on Twitter.
Links for this Episode :
MTM Listener Survery
Merry Buckley on twitter
Carl Zimmer website
Carl Zimmer on TWiV
She has her Mother’s Laugh
099: Microbial engineering for biofuels and beyond with Wayne Curtis
2019/01/11
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How does an engineer approach microbial genetics? cworks with microbes of all kinds to optimize metabolic and agricultural systems. Here he discusses his work with Rhodobacter to make biofuels and for membrane protein expression, with Agrobacterium and plant pathogenic viruses to make drought-resistant plants, and with Clostridium and yeast cocultures for lignocellulose digestion.
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Full shownotes at asm.org/mtm
Links for this Episode :
Wayne Curtis Lab site at Penn State University PLoS One : Molecular Cloning, Overexpression, and Characerization of a Novel Water Channel protein from Rhodobacter sphaeroides Protein Expression and Purification : Advancing Rhodobacter sphaeroides as a Platform for Expression of Functional Membrane Proteins Biotechnology for Biofuels : Consortia-Mediated Bioprocessing of Cellulose to Ethanol with a symbiotic Clostridium phytofermentans /Yeast Co-Culture HOM Tidbit: Genentech “Cloning Insulin” blog HOM Tidbit: Genentech press release announcing insulin cloning
098: Insect and human microbial symbionts with Seth Bordenstein
2018/12/30
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Over the course of a few decades, scientists have learned how insect endosymbiont bacteria affects insect reproduction and have used this understanding to control mosquito-born diseases. Seth Bordenstein talks about his research on the insect endosymbiont Wolbachia , human-microbiome interactions, and how the ecosystem of a host and its microbes can be refered to as a holobiont.
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Links for this Episode :
Bordenstein Lab at Vanderbilt University mSystems: Getting the hologenome concept right: an eco-evolutionary framwork for hosts and their microbiomes. PLoS Biology : Gut microbiota diversity across ethnicities in the United States . PNAS : One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster . Discover the Microbes within! The Wolbachia Project HOM Tidbit: Studies on Rickettsia-Like Micro-Organisms in Insects (1924 paper from Hertig and Wolbach)
097: The Cool World of Glacial Microbiology with Christine Foreman
2018/12/13
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Christine Foreman explains how microbes can survive and grow on glaciers, and what we can learn from microbes in glacier ice cores.
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Julie’s Biggest Takeaways
Liquid inclusions between ice crystals create a vein-like network that allow microbes to survive between the ice crystals.
Microbes living in glaciers have to adapt to a number of extreme environments: low water, low nutrients, extreme cold, and 6 months each of full sun or complete darkness mean there are many adaptive requirements to live in glaciers.
Air bubbles trapped in ice cores provide data on the atmosphere 40,000 or 100,000 years ago. Using very old samples like these can inform scientists about the precipitation, temperature, and major cataclysmic events that occured at those time periods.
Because so many researchers share ice core samples, a research group like Foreman’s will often get a very small sample, as low as 7 ml, for a particular time period. Given that there are only 100 to 10,000 cells per ml, that is not a lot of sample to work with!
Aggregation of life, including microbial biofilms, changes the absorption of solar radiation. A clear, white surface radiates back as much as 90% of the solar radiation, but as aggregates form, they allow more of the solar radiation to be trapped. This in turn can increase microbial metabolic activity and allow even more microbial growth, leading to a feedback loop that increases absorption of solar energy and loss of glacial surfaces.
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096: HIV interaction with the immune system with Mark Connors
2018/11/30
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A very small proportion of people infected with HIV do not develop AIDS. Mark Connors talks about 2 patient populations that his lab studies, the elite controllers and the elite neutralizers, who control HIV infection with their respective T cell or B cell responses. Connors hopes his work on killer T cells and broadly neutralizing antibodies will help scientists develop better HIV therapies or an effective HIV vaccine.
Links for This Episode :
Mark Connors labsite at NIAID Immunity article: Identification of a CD4-binding-site antibody to HIV that evolved near-pan neutralization breadth. Immunity commentary: Class II-restricted CD8s: New lessons violate old paradigms. Science article: Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Imagining an HIV-Free Future (Smithsonian Worlds AIDS Day Event (Live Dec 4th at 6:45pm) HOM Tidbit: 12 Diseases that Changed Our World MTM Listener Survey
095: The Evolution of Virulence with Andrew Read
2018/11/15
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In the early 2000s, Andrew Read predicted that non-sterilizing vaccines would lead to more virulent disease. He was able to test his hypothesis with the real-world example of Marek’s disease, a disease of chickens. Read tells the story of his discovery, and talks about his work on myxoma virus.
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Julie’s Biggest Takeaways :
Every chicken on the market is vaccinated against Marek’s disease. Infection with Marek’s disease causes tumors on the bird and can lead to direct death, or condemnation of a flock requiring their culling. Birds are vaccinated with a live, attenuated virus, and there have been 3 vaccine iterations. The first used a related herpesvirus isolated from turkeys, while the second vaccine added a second virus strain. Each of these vaccines conferred protection for about 10 years, after which the disease began popping up again. The 3rd generation vaccine added yet another serotype - this additional strain is a mutant strain of the chicken-infecting serotype - and has been effectively protecting chickens since the 1990s.
Chickens do not get sterilizing immunity from the Marek’s disease vaccine; they can be infected by the wild-type virus, but the vaccine prevents infected animals from having disease symptoms. These asymptomatically infected animals can still shed the virus. Contrast this to human immunity from many of our vaccines, such as measles or smallpox vaccines, in which our immune response stops the virus from entering our cells and therefore blocks virus replication.
Vaccination inhibits strains with lower virulence more than strains with higher virulence. This fact, combined with asymptomatic infection, means that although the infected birds don’t show disease symptoms, they are more likely to be shedding more virulent (or ‘hot’) strains. This generates selection for these hot strains that wouldn’t normally be successful. Without vaccination, host strains kill the host too quickly to allow viral replication and transmission to occur; Vaccines allow these hot strains to propagate.
Vaccine resistance is much more rare than antibiotic or antimicrobial resistance. This is due to a number of factors, including the diversity of microbial population being acted upon (small with initial infection, large when treated with antimicrobial drugs). Vaccines are much more evolution-proof for these reasons.
Purposeful release of myxoma virus during the 1950s in Australia killed between 10 and 100 million animals, or 99.9% of the rabbit population. Frank Fenner followed the virus and surviving rabbit populations and discovered that myxoma viruses that were too virulent were less likely to be transmitted, because they killed the host too quickly. He also showed that the small surviving number of rabbits were more resistant to viral infection. The arms race between the two has generated a virus so immunosuppressive that Read’s group has found the currently circulating myxoma virus has changed the way it kills its host: the virus disables the rabbit immune system and allows the rabbit’s own microbiome to cause invasive bacterial disease.
094: Containing a Nipah virus outbreak with G Arunkumar
2018/11/01
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A recent Nipah virus outbreak in Kerala, India, was halted due to improved detection capabilities. G. Arunkumar tells the story of his involvement.
Host: Julie Wolf
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Julie’s Biggest Takeaways:
Because bats are the normal reservoir, Nipah virus outbreaks appear to be seasonal, with an increase in cases coinciding with the spring, when the bat reproduction season is.
Once a person is infected through direct contact with the virus, the virus is transmitted person-to-person through respiratory droplets.
Family clusters combined with the right incubation time acted as a clue that a Nipah virus outbreak had begun.
Molecular tests improved virus detection during the 2018 Nipah outbreak because patients presented symptoms within a few days, which was too short for them to have developed antibodies. Molecular tests allowed identification of infected patients within days. Previous outbreaks have taken weeks to months, or even years, to identify the infectious virus.
A single crossover event in the recent Nipah outbreak led to person-to-person transmission within the 22 additional individuals. Hospital infection control practices are important to reduce transmission to healthcare workers and hospital attendants.
Featured Quotes:
“Most of the Nipah outbreaks, you find a lot of hospital transmission from the infected patient to healthcare workers, the other patients in the ward as well as the patient attendants.”
“The only virus that can cause encephalitis in a family cluster is Nipah. With other encephalitis viruses like herpes or Japanese encephalitis virus, you don’t see family clusters.”
“Nipah virus is a level 4 pathogen, so the cultivation can be only done in a level 4 laboratory. But molecular tests allow you to test for it at a lower level laboratory, such as a BSL-3 lab, because you inactivate the virus. You are only focusing on RNA. The risk can be reduced.”
“When you use serological diagnosis, the antibodies are detectable only after 8-10 days after onset of illness. Nipah is a very, very acute, serious fatal disease. Many people may die before they develop antibody. So we need to use a combination of real-time PCR and antibody.”
“This is the first time in the history of Nipah that the diagnosis was done in country. All the previous diagnoses were done at CDC Atlanta.”
Links for This Episode:
Department of Virus Research at Manipal Academy of Higher Education Journal of Clinical Microbiology Review on Nipah virus ASM Global Impact Report HOM Tidbit: NPR piece interviewing K. B. Chua and others
HOM Tidbit: Science article first describing Nipah virus
093: Biofilms and metagenomic diagnostics in clinical infections with Robin Patel
2018/10/18
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Robin Patel discusses her work on prosthetic joint infections and how metagenomics is changing infectious disease diagnostic procedures.
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Julie’s Biggest Takeaways :
The term antimicrobial resistance can mean many things. Although acquisition of genetic elements can lead to drug resistance, so can different growth lifestyles of bacteria; the same bacteria growing in liquid culture may be more susceptible to a drug than those bacteria growing on a biofilm. Lifestyle and genetics can intertwine, however, when bacteria growing as a biofilm exchange resistance genes through horizontal gene transfer.
How do bacteria reach an implanted surface, such as on a prosthetic joint, to cause infection? It may rarely occur during surgery, if even a single bacterium reaches the joint surface despite the sterile conditions; alternatively, it could occur through hematogenous spread (through the blood) after the surgery is over. Most infections are believed to be seeded at the time of implantation.
While scientists don’t perform teeny, tiny implants in animal models of infection, the materials are placed in animal bone to mimic as similar an immune response as possible.
Targeted metagenomics and shotgun metagenomics are both being developed clinically. Targeted metagenomics looks at one specific gene found in a number of species, such as the 16S ribosomal RNA gene. Shotgun metagenomic looks at all DNA present, and requires a lot more cleaning up to eliminate human genomic material, which is the major sequence of any human-derived sample.
092: A new type of malaria vaccine utilizing the mosquito immune system with Carolina Barillas-Mury
2018/10/05
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To eliminate malaria, you have to stop transmission, and that’s what Carolina Barillas-Mury hopes to do. Her work on the interaction of the malaria parasite Plasmodium falciparum may lead to a transmission-blocking vaccine. She explains how, and discusses the co-evolution of malaria, mosquitos, and man.
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Julie’s Biggest Takeaways:
When born, babies carry antibodies from their mothers, which may protect them through passive immunity; additionally, babies are more easily protected from mosquito exposure by placing them under bed netting. As they grow, children become more active, and their passive immunity concurrently wanes. They may be exposed to mosquitoes carrying malaria parasites and their still-developing immune systems aren’t able to keep the parasites from replicating, leading to more severe disease, including cerebral malaria.
The Culicines and Anopholines are two major groups of mosquitoes that carry disease. The culicines have recently spread around the world, but the Anopholines species moved from Africa into South America one hundred million years ago, but malaria only moved into the New World a few hundred years ago with the slave trade. The relationship between the mosquitoes and malaria parasites has been evolving much longer in Africa than it has been with the specific population of mosquitoes in South America - one of the reasons why the disease is less devastating in South America.
The ‘invisibility gene,’ pfs47 , is expressed in the banana-shaped ookinete and helps the malaria parasite to avoid detection by the mosquito immune system. The pfs47 malarial gene is adapted for the localized mosquito populations from the same region as the parasite; if an African mosquito is infected with a South American parasite, the parasite is more likely to be recognized and killed than if the African mosquito is infected with an African parasite.
The most immunogenic proteins in parasites may produce an immune response, but this immune response may not block infection. New vaccines are concentrating on where antibodies bind, to ensure there is a biological effect of the immune response, and this is why Barillas-Mury has used a modified Pfs47 protein to generate immune responses, rather than its native form.
Links for this Episode:
Carolina Barillas-Mury NIAID website NPJ Vaccines: Antibody Targeting of a Specific Region of Pfs47 Blocks Plasmodium falciparum Malaria Transmission. PLoS One: Molecular Analysis of Pfs47-Mediated Plasmodium Evasion of Mosquito Immunity. PNAS: Plasmodium Evasion of Mosquito Immunity and Global Malaria Transmission: The Lock-and-Key Theory. HOM Tidbit: History of the Discovery of the Malaria Parasites and their Vectors MTM Listener Survey
091: SARS and MERS coronaviruses with Stanley Perlman
2018/09/20
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How do researchers study a new pathogen? Stanley Perlman talks about how virus researchers studied SARS and MERS after they emerged, what they learned, and why there are no more cases of SARS. He also discusses his work on a coronavirus model of multiple sclerosis.
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Julie’s Biggest Takeaways :
Coronaviruses have the largest RNA genomes, with up to 40 kB of sequence, but why their genomes is so big is unclear - their genomes don’t seem to code for more genes than viruses with smaller genomes.
Before the SARS coronavirus outbreak in 2002, few severe human infectious coronaviruses were known, but the several coronaviruses had been identified that cause serious disease in animals such as pigs, cats, and cows.
Where did SARS go? SARS coronavirus had to cross into people and mutate for better infectivity, and when infecting people, it caused a lower respiratory disease. Quarantining SARS patients is extremely effective because the symptoms coincide with infectivity, and spread of SARS was quenched by strict use of quarantine. Quarantine is less effective for diseases like influenza or measles, because patients are contagious before showing symptoms.
Because of its low person-to-person transmission, there’s very small possibility of major outbreaks from large gatherings such as the Hajj. MERS acts more like an opportunistic infection, and its transmission among people has been mostly among immunocompromised or otherwise sick people in the hospital.
By the time patients present with multiple sclerosis, it may be 20 years after an inciting event that triggers the disease. By using a murine coronavirus inciting event for neuron demyelinization in mice, the role of the immune system in this process can be interrogated. Scientists may not understand the exact cause of MS in people, but this model helps them to understand how different immune cells contribute to disease.
090: Using yeast to generate new chocolate and beer flavors with Kevin Verstrepen
2018/09/06
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You may know that beer is fermented, but did you know making chocolate requires a fermentation step? Kevin Verstrepen discusses how his lab optimizes flavor profiles of the yeast used in this fermentation step, and explains how yeast was domesticated before microorganisms had been discovered.
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Julie’s Biggest Takeaways :
Microbes are used to ferment foods, but they do more than just add ethanol or carbon dioxide: their metabolic byproducts add flavors and aromas that are an essential part of the fermented food.
In cocoa bean fermentation, the yeast that are part of the initial fermentative microbial population control the development of the subsequent microbial populations and the quality of the final product.
How the volatile flavor compounds generated during fermentation survive the roasting step remains unclear. Heat can destroy these labile compounds, but Kevin thinks the compounds were able to survive roasting because they become embedded in lipids (fat) of the cocoa beans. Similar compounds produced during bread rising are destroyed during baking, possibly because there is less fat to protect these molecules.
Mixing data science and beer: a computer scientist in the Verstrepen lab analyzed the flavor profiles of several hundred beers, which were also analyzed by a trained tasting panel. The goal is to link the chemistry to the aroma, which requires complex algorithms due to the integration of hundreds of flavor molecules.
A spontaneous hybridization between Saccharomyces cerevisiae , the normal fermentative yeast, and S. eubayanus , a cold-tolerant yeast, resulting in a hybrid that can ferment at colder temperatures, as is required for brewing lager beers. There are 2 lineages that are used by most breweries, and while different characteristics have evolved over time, the genetic bottleneck limits characteristic diversity. The Verstrepen lab made several crosses between these two species and selected for hybrids that generated those with desirable characteristics. Molecular means can determine the offspring that are most likely to confer desired characteristics, but the commercial yeasts are not specifically genetically manipulated to this end.
Domesticated yeast have different characteristics than their wild counterparts. Domesticated yeasts have lost the ability to use certain sugars, but have gained abilities associated with their use; beer yeasts use maltose at much higher rates, for example. When the origins are traced using molecular methods, it goes back to medieval times. How to domesticate an organism that hasn’t been identified? Brewers have long transferred sediment from one batch of beer into new batches, which is how selection for human-desired characteristics began. Wine yeasts, which are not passaged but are likely inoculated from the same vineyard annually, show less domestication than the beer yeast.
089: Using the zebrafish microbiome to study development and the gut-brain axis with John Rawls
2018/08/23
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How can the humble zebrafish teach us about the human microbiome? John Rawls discusses the benefits of using animal models
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Julie’s Biggest Takeaways:
Zebrafish and other model animals provide opportunities to understand host-microbe interactions. Zebrafish are particularly useful for imaging studies, due to their translucent skin and the ease of in vivo microscopy. This allows zebrafish to be used to in studies of spatial architecture or longitudinal studies (imaging the same fish specimen over time) in ways that other model organisms can’t be.
Zebrafish get their first microbes from their mother, just like mammals! The chorion, a protective coating that surrounds the zebrafish embryo, is seeded with microbes from passing through the cloaca of the female zebrafish. Surface-sterilizing this chorion allows researchers to generate germ-free animals that are very useful for microbiome studies.
A gut epithelial transcription factor is regulated by a signal from the gut microbiota, and this signaling interaction is conserved among all vertebrates. The transcription factor itself, HNF4, is found in both complex and simple animals, like the sea sponge, and may serve a long-conserved function in regulating interactions between animals and their microbiota.
Enteroendocrine cells release hormones based on specific chemical cues, but they can also interact with the nervous system. This makes them an important part of the gut-brain system, and the power of in vivo imaging has made zebrafish a great model for better understanding their function. Specific members of the microbiome specifically stimulate these EECs, sending signals up the vagus nerve to the brain.
Featured Quotes:
“We know that the zebrafish functionality of its intestine is very similar to what one encounters in the mouse or human intestine and we and others have been able to translate our findings from zebrafish studies into human biology.”
On genomic studies that have found similar transcription profiles in zebrafish, stickleback fish, mice, and humans: “This suggested that there is a core transcriptome that gut epithelial cell use in different vertebrate species that haven’t shared an ancestor in 420 million years!”
Comparing fish and mouse: “Genes regulated by microbiota in these respective hosts display a lot of overlap. Many of the same signaling pathways and metabolic processes are affected by microbiotas in different hosts in similar ways.”
“There’s been a lot of interesting research documenting the role of the intestinal microbiome in promoting harvest of dietary nutrients we consume. Much of that literature has been focused on the events that occur in the distal intestine, in the colon, where recalcitrant carbohydrates and proteins that make it that far, many of which we are unable to digest, are made available to the colonic microbiome, members of which are able to digest and degrade them to things such as short chain fatty acids, which we can consume.”
“Eventually, we’ll have some strong candidates in terms of specific bacterial strains or communities or factors or pharmacologic agents that could be used to affect dietary fat absorption or metabolism. We’re still a long ways away from that.”
“One of the fascinating things about developmental biology is that the only way you get a viable animal is if the different tissues and the different cells within the body are coordinating amongst themselves for energy, for nutrients, for oxygen, et cetera. As you’re building an animal and as you’re sustaining an animal, the different tissues have to cooperate. When that doesn’t happen, when tissues or cells become selfish or don’t play by the rules, you get things like cancer and other diseases as well...when I began learning about the field of microbiome science and some of the work that was coming out from that field, it sounded to me like the microbiome was going to be a really important part of that. Not only can we think of the microbiome as a ‘microbial organ,’ as it is sometimes called, and therefore worthy of consideration within the context of developmental biology, but also the influence of the microbiome on any one tissue is going to modify its need and its ability to cooperate within the integrated system.”
Links for this Episode:
John Rawls’ lab website More amazing zebrafish images from the Rawls lab Duke University Microbiome Center Genome Research article on HNF4 regulation Cell Host and Microbe article on microbial influence on fatty acid absorption
088: Using Bacterial Structures as Nanowires with Gemma Reguera
2018/08/10
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Gemma Reguera discusses her studies of Geobacter pili, which transfers electrons to iron oxide and other minerals, and can be used for new biotech applications.
Host: Julie Wolf
Subscribe (free) on Apple Podcasts , Google Podcasts , Android , RSS , or by email . Also available on the ASM Podcast Network app .
Julie’s Biggest Takeaways :
Geobacter sulferreducans , a bacterium that “breathes” rust, is the lab representative of the genus Geobacter that dump electrons onto rust. These specialized microbes use minerals like manganese oxide and iron oxide (also known as rust) for respiration in both terrestrial and aquatic sediments. Although many species are strict anaerobes, a few species can grow under microaerophilic conditions, in which the bacteria will respire the oxygen to eliminate its toxic effects on the cell.
Iron oxide respiration relies on the Geobacter pili, a simple structure composed of a single peptide repeat. The pili concentrate on one side of the bacterial cell, where they connect the cell with the iron oxide to release the electrons that have been accumulating. The pili immediately depolymerize and retract, shedding the mineral before returning into the cell.
Mass-producing pilin subunits in E. coli took a bit of trouble shooting, but now Reguera and her colleagues can make them on a much larger scale, which bodes well for expanding tests into electronic applications.
Commercialization grants address the “valley of death,” the chasm between the technologies developed at the bench and the scale of production necessary for industrialization.
Geobacter can bind and reduce many minerals using their pili, including uranium and other toxic heavy metals like lead and cobalt. Using Geobacter pili in agricultural soils or aquaculture waters may help remove these contaminants and improve the health of these ecosystems.
Featured Quotes :
“I remember when I started as a microbiology student, I think I underappreciated the role that electrons and the movement of electrons play in microbiology.”
“There is absolutely not a single process in living organisms that is not energized by the movement of electrons.”
“The Earth didn’t have oxygen for the first 2 billion years, if not longer - and there was life! On Earth! Those early organisms were really great at finding minerals, metals, just about anything other than oxygen to dump their electrons, continue to grow, and to colonize the Earth.”
“When you start comparing the structure and the amino acid composition of this subunit to any other known bacterial pilins, you really see 2 remarkable changes: one of them is the pilin of Geobacter is very small. the second is that little stick has aromatic amino acids. When the sticks come together to make the filament, they cluster very close to each other and create like a staircase for the electrons to move fast. It’s like a magic combination in which you have the right structural reduction and the right amino acids to really fit like a puzzle to create paths for electrons.”
“What has always motivated me is learning something new.”
Links for This Episode :
Gemma Reguera lab website Gemma Reguera interview on “People Behind the Science” HOM: Thirty-Second Annual Meeting of the Society of American Bacteriologists
HOM: Barney Cohen: An Appreciation (Bacteriological Reviews memorial)
087: Legionnaire’s Disease with Michele Swanson
2018/07/25
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Why do Legionnaire’s Disease outbreaks occur mostly in the summer? What is the connection of the Flint change in water source and Legionella outbreaks in the area? Michele Swanson discusses her work on Legionella pneumophila and her path from busy undergraduate to ASM President.
Julie’s Biggest Takeaways:
Legionella pneumophila is a waterborne microbe that lives in fresh water and can colonize water systems of the built environment. Colonization of cooling systems, like those used in air conditioning systems, can lead to contaminated water droplets that can cause disease.
Legionella are very adaptable to different environment, but scientists don’t have great models to determine the exact preferences of the bacterium.
After Flint switched water sources from lake to the Flint river, a chemical that prevents corrosion was omitted from the water treatment. This led to lead in the water, which was detected in pediatric patients. An increase of legionella cases in the two years also occurred, and the question was whether the outbreak was related to the shift in water chemistry. Michele joined a team of water engineers, epidemiologists and sociologists to answer this question, and the team found an association between low chlorine levels and high risk of legionella disease.
Across the globe, more than 80% of disease is associated with L. pneumophila serogroup 1. The serogroup is based on the bacterial lipopolysaccharide (LPS) structure, which in this strain is very hydrophobic and may allow this serogroup to withstand a higher degree of desiccation than other strains. A urine-based diagnostic test works well, but only to detect serogroup 1. The strain isolated from patients of the Flint outbreak were serogroup 6, as were Legionella isolated from the homes of Flint residents.
Featured Quotes:
“Amoeba are very good at digesting bacteria, eating them for food, but Legionella , because it’s been under this severe selective pressure of the amoeba, they’ve evolved tools to allow them not only to survive within the amoeba but to replicate within the vacuole of the amoeba.”
“We now have equipment that throws water into the air and gives [ Legionella ] a new opportunity to be ingested by a macrophage. It can then deploy the same tricks it uses to grow inside amoeba to grow inside the macrophage.”
“[Human infection] is a tragedy for the patient, but also for the microbe...humans are a dead-end for the bacterium.”
“I was really delighted to be recruited to work with this interdisciplinary team on a public health crisis here in my home state. It has opened my eyes to a much more complex pathway and I just feel really privileged in this stage in my career to be able to turn my attention to these larger public health issues.”
“People want to hear encouragement; we have a tendency to compare ourselves to those who are 5-10 years ahead of us. Encouragement really is valuable.”
Links for this Episode:
Michele Swanson at the University of Michigan
mBio : Prevalence of infection-competent Legionella pneumophila within premise plumbing within southeast Michigan
PNAS : Assessment of the Legionnaire’s disease outbreak in Flint, Michigan
Microbial Sciences blog post: Examining Flint: New research highlights lack of Legionella public policy
ASM membership
086: Toxoplasma gondii and neuro-invasive disease with Anita Koshy
2018/07/12
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How is Toxoplasma gondii , a protozoan that causes neuro-invasive disease, transmitted as a foodborne pathogen? Why are cats important in transmitting Toxoplasma infection? Anita Koshy answer these questions and talks about her research on the latest Meet the Microbiologist.
Julie’s Biggest Takeaways :
The primary host for T. gondii is cats, in which the protozoan can undergo sexual reproduction. Why cats? No one knows, in part because there isn’t a good in vitro system to study cat epithelial cell interactions with T. gondii .
Most warm-blooded animals, including birds, can be infected with Toxoplasma . Intermediate hosts can pass Toxoplasma from one to another if one eat these tissue cysts, explaining why Toxoplasma can be a foodborne pathogen.
In healthy individuals, the immune response clears most fast-growing cells (tachyzoites) but some protozoans convert to a slow-growing cell form (bradyzoites). In people, these bradyzoites form cysts predominantly in the brain, the heart and the skeletal muscle.
Some serological studies suggest a tie between Toxoplasma infection and brain disorders, but these are less definitive than causative studies in mice. Populations with high Toxoplasma or low Toxoplasma prevalence don’t see a correlative incidence of disorders such as schizophrenia or Alzheimer’s disease.
Featured Quotes :
“When we talk about neuroinfectious diseases, we’re talking about the diseases that cause symptoms. Those that can get into the central nervous system and those that cause symptomatic disease are the same.”
“A parasite is sitting there dormant or maybe reactivating every so often and the immune system comes in and deals with that reactivation. But when you lack an immune system, all of a sudden when that parasite reactivates, there is no longer this immune system that will come in and clear it out.”
“What we don’t know is whether reactivation occurs preferentially in the brain. There is evidence from HIV patients of inflammation of the heart or inflammation of the skeletal tissue - but those weren’t the symptoms that presented, which were of the brain. Did reactivation happen in the brain, or did it occur elsewhere and the parasite was able to travel to the brain and there’s no longer an immune system to clear it out?”
Links for this Episode :
Koshy Lab Site Sea Otter Infection with Toxoplasma Rats Infected with T. gondii Lose Their Aversion to Cat Urine HOM Tidbit: The History of Toxoplasma gondii Bill Hutchinson obituary
085: Using DNA technologies to answer epidemiological questions with Jennifer Gardy
2018/06/21
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Jennifer Gardy talks about whole-genome sequencing as a technique to address public health issues using genomic epidemiology. She talks about her research on TB and new DNA sequencing technologies, including her vision for microbial genetic sequencing as one piece of the puzzle in the future of public health.
Julie’s Biggest Takeaways :
Whole-genome sequencing technologies are replacing older DNA technologies to identify relatedness between microbial isolates. The genome sequences help to identify epidemiological questions such as the origins of an outbreak.
A pathogen’s genome being passed person-to-person accrues small changes, similar to children playing telephone - except those children are scattered around the room, and you have to logically deduce the order in which the information was passed.
DNA sequencing has moved forward faster than the upstream genomic preparation and downstream sequence analysis areas; Gardy expects advances in these ‘bookend’ areas to be breakthroughs of the future.
The Ebola and Zika outbreaks were test cases for portable DNA sequencing technologies, but informative based on the different disease presentation: Ebola patients have high viral loads and thus a lot of genomic material, but Zika patients have much lower viral loads and it was much harder to get samples.
Based on pathogen characteristics, DNA sequencing can identify the end of an outbreak. Gardy used sequencing to find that patients with TB, which can take years to develop into fulminant disease, had been infected years previous, and was able to see that transmission was no longer ongoing.
Featured Quotes :
“Genomics is really cool because instead of interviewing people about what happened in an outbreak, we’re interviewing the pathogen!”
“[Working at BCCDC] is a really nice ecosystem, where you can really see the results of your research changing public care policy and practice in real time, and that is incredibly rewarding.”
“The only prediction you can make about DNA sequencing is there’s always going to be something new and different.”
“Depending on your use-case, sometimes you need to go after the whole genome and other times a targeted approach is more than enough.”
“I’m excited to see how this [microbial DNA sequencing] work fits in into an overall public health landscape. It’s cool to sequence genomes and make some reports about transmission networks, but that’s just one small part of a very big public health system that is trying to keep populations healthy. It requires so many different people, from nurses and doctors on the frontline to policy makers behind the scenes to social scientists who are interacting with patients or care providers to people that are understanding the economics of these things... when you start to see how these different pieces of the puzzle fit together, I think there’s a lot of opportunities in the future for making microbial genomics just one piece of a large interdisciplinary puzzle of people that are working together across different fields to address a disease from multiple different angles.”
Links for This Episode :
Jennifer Gardy’s website Jennifer Gardy at UBC Nanopore Minion Alan Alda Center for Communicating Science Banff Science Communications HOM Tidbit: Albrecht Kossel, a Biographical Sketch
084: How viral-bacterial interactions influence viral infection with Julie Pfeiffer
2018/06/07
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See the full shownotes at: asm.org/mtm
Julie Pfeiffer tells the story of how she serendipitously found a role for the gut microbiota during polio virus infection, and how she and her lab discovered an important role for bacterial glycans in viral biology. She also talks about viral fitness strategies, and how RNA viruses and DNA viruses benefit from making different amounts of errors when copying their genomes.
Julie's biggest takeaways:
Determining the exact nature of the glycans that play these roles has been difficult because they are very complex. Aspects of lipopolysaccharide, chitin, and peptidoglycan are all sufficient to bind the viral capsid, but because of their structural complexity, it’s difficult to pinpoint the exact molecular interaction.
Bacterial glycan interactions with viruses benefit the virus in two ways: the virus can be delivered to a host cell it will infect, and the viral capsid is stabilized. Whether there is a benefit to the bacterium during these interactions is unknown, but is an active area of research in Julie’s lab.
Many viruses can be inactivated at body temperature or even room temperature if they prematurely release their genetic material. Polio viruses are simply a protein shell surrounding an RNA genome, and the capsid can ‘breathe,’ slightly changing its conformation. Sometimes, the genome is accidentally released, resulting in a viral dead end. Julie showed that bacterial glycans will lock the capsids into a conformation and prevent genome release from happening until the virus encounters a host cell.
Julie is a proponent of clear communication, including with those working in similar fields, which she learned from her experience as a postdoctoral fellow. She and a postdoc in a different institution, Marco Vignuzzi, independently isolated a polio virus mutant that made fewer in genome replication. Both showed that the virus had a defect during mouse infection, indicating that the ability to introduce errors during genome replication is beneficial to viral fitness. Julie and Marco finally met at a viral evolution conference, after which they became close friends.
Featured Quotes (in order of appearance):
“I get more excited about a surprising result because it probably means there’s some interesting underlying biology that couldn’t be anticipated!”
“We’ve done many gross experiments, so buyer beware; you’ve got to know what you’re getting into [with a fecal-oral pathogen].”
“The infectious unit may be more complicated than we think!”
“Communicating with people you know working on similar things can be mutually beneficial for everyone: you both get credit; nobody gets scooped. It’s win-win for sure.”
“The truth is most enteric viral infections are self limiting in most healthy individuals so you’re much better off trudging through a day or two of gastrointestinal illness than blowing up your microbiota.”
Links for this episode
Julie Pfeiffer website at UT Southwestern Medical Center Back-to-back Science publications from Golovkina and Pfeiffer PLOS Pathogens: The importance of model systems: Why we study a virus on the brink of global eradication Viruses and Cells Gordon conference (donate here )
HOM Tidbit: Michael Underwood’s A Treatise on the Diseases of Children
083: Microbial communication via quorum sensing with Pete Greenberg
2018/05/24
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Pete Greenberg tells how bacteria can communicate based on cell density, a phenomenon he helped name quorum sensing. He talks about therapeutics based on quorum-sensing discoveries, and how studying bacterial interactions can be used to test ecological principles like cooperation and social cheating.
Julie's biggest takeaways:
Quorum sensing can be likened to an old-fashioned smoking room, where a few cigar smokers don’t affect the air quality, but as more smokers enter the room, it becomes beneficial to the group to open the window: a changed behavior that benefits the group environment.
Differentiating waste molecules from signaling molecules is important to define specific quorum sensing. The experimental evidence that shows that molecules serve as quorum sensing signals that allow bacteria to respond at high density comes from social engineering experiments to identify ‘cheaters.’
Quorum sensing results in changes in gene expression that benefit the community but not necessarily individual cells. An example is antibiotics, which when made by a single cell aren’t at a high enough concentration to kill competitor microbes. As a group, all cells working together can produce a cloud of antibiotic that may be able to protect from competitors.
The ability of microbes to receive or ‘eavesdrop’ on the signals produced may be cooperative, but is more likely competitive, giving the eavesdropper a competitive advantage by informing them about another species’ presence.
If you knock out quorum sensing, you get abnormal biofilms, but it doesn’t ablate biofilms completely.
Although a self-described disinterested high-school student, Greenberg signed up for a weekend field trip to get out of a test on a Friday. It was looking at animals in the intertidal bay of the Pacific Northwest that inspired him to be a biologist! Greenberg also credits his broad biology undergraduate training for preparing him to apply socioecology concepts to bacteria.
Quorum sensing was originally called ‘auto induction.’ In the early 1990s, Greenberg was writing a minireview for the Journal of Bacteriology and wanted to think of a catchy title. As Greenberg remembers, coauthor Steve Winans explained the concept to his family, and his brother-in-law said “it’s like the bacteria need a quorum” - the birth of the term ‘quorum sensing.’
Featured Quotes (in order of appearance):
“So-called ‘cheaters’ don’t respond to the signal, they’ve lost the ability to respond to the signal. The product that’s useful for the common good any more. They don’t pay the cost of cooperation but they can benefit by the cooperative activity of everyone else in the community...there’s a fitness advantage for cheaters in this environment.”
“It’s a real case of convergent evolution. It’s important that the bacteria can do this, and these two really distinct types of [gram-positive and gram-negative] bacteria have evolved completely different mechanisms to perform quorum sensing.”
“I think of bacteria as a way to study what is called ‘Darwin’s dilemma.’ If a cheater emerges among a population, it will have a fitness advantage over the population of cooperators. It should take over the population and ultimately cause the tragedy of the commons, where there are too many cheaters and not enough cooperators and the whole system collapses. Darwin’s dilemma is: how is cooperation stabilized? We know it exists and it seems like it shouldn’t - we can use bacteria to get at the rules.”
“I got interested in [quorum sensing] because it was so cool!”
“I had this idea, as we began to unravel quorum sensing in these marine luminescent bacteria, that any idea in biology that’s a good idea will occur more than once - but I didn’t have any evidence of that. For 15 years, my lab and essentially one other lab, Mike Silverman’s lab, were the only labs working on this. It was really the early 90s when our group and other groups started to realie that lots of bacteria do this. It’s one of those fantastic oddesies. It’s luck - luck and hard work, I guess. Hard work by the people in my lab as I sit around as watch!”
“It’s funny how a term can catch on and sort of crystallize a field! But somehow, it seemed to do that. I’ve gotten really into trying to think of catchy terms since then, and the latest one is ‘sociomicrobiology,’ which I introduced with Matt Parsek about 12 years ago and there’s a burgeoning field called sociomicrobiology. I’m trying to think of another term now, before I retire!”
Links for this episode
Pete Greenberg lab at the University of Washington Pete Greenberg 2004 PNAS bio Journal of Bacteriology minireview: Quorum Sensing in Bacteria HOM: Woody Hastings memoriam ASM Podcasts
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
082: The struggle to study hepatitis C virus with Charlie Rice
2018/05/11
Charlie Rice gives the history of learning to grow hepatitis C virus in culture, from pitfalls to hurdles and successes along the 20-year journey. He also talks about yellow fever virus, its vaccine, and the importance of curiosity-driven research
081: Developing infectious disease diagnostics with Melissa Miller
2018/04/26
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How are new diseases detected in a clinical microbiology lab? Melissa Miller talks about the time it takes to develop a test for a new disease (hint: it’s getting shorter). She also shares her definition of ‘point-of-care’ diagnostics and explains the major trends for clinical microbiology labs.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Antibiograms are vital to understand the resistance characteristics of locally circulating disease strains. These help make empirical decisions for antibiotic therapy regimens before the susceptibility test results are available.
New diseases require new diagnostic tests. How to determine how well new tests work once they’re developed? Clinical microbiologists look to the sensitivity (how well does a test detect if a patient has a disease) and specificity (how often is the test negative if the patients doesn’t have it) of the test. Having access to positive controls (that is, samples from a patient known to have the disease) can prove difficult in some settings, such as in North Carolina, where no Zika patients were admitted while the Zika virus test was being developed.
When the HIV epidemic was beginning, it took several years after the HIV virus was identified to sequence its genome and use this for molecular testing. In 2002-2003, it took just over a month to get the SARS genome sequence for use in developing assays. It’s even quicker today; within a week, we can have sequences from viruses around the world.
Defining ‘point-of-care’ testing took an entire hour at a recent American Academy of Microbiology colloquium! Melissa’s take: It’s a test that can be done at or near to where the patient is.
Point-of-care tests are exciting but can also pose challenges. A recent example is false-positive pertussis tests that were shown to be due to pertussis vaccine being administered nearby. Ensuring the tests are used safely and accurately will best serve healthcare workers and patients alike.
Molecular diagnostics have two trends: one trend simplifies existing technologies into point-of-care tests. The other trend adds complexity, by applying next-generation sequencing techniques in a reproducible manner.
Featured Quotes (in order of appearance):
“Laboratorians are often in the basement or in a setting where they aren’t visible to the healthcare team, but they’re very vital to taking care of the patient.”
“When you’re using laboratory-developed tests, the way it works in one laboratory may be very different from how it works in another laboratory.”
“The ultimate goal [of point-of-care testing] is to get a result that’s actionable. We don’t need to do tests that aren’t going to result in a clinically actionable decision.”
“In many ways, the technology is ahead of where our quality assurance protocols are.”
“I think it’s going to be very important in going ahead that we continue to have laboratorians involved in developing these point-of-care programs and consulting to these sites, helping to make sure that there are policies and procedures that ensure quality results for their patients.”
“It’s one thing to do it in a research setting; we’ve collaborated with a number of folks using next generation sequencing. But to then move it to the clinical lab and have it be reproducible and have the quality at the level you need for a clinical lab is a completely different challenge.”
Links for this episode
Melissa Miller University of North Carolina Website Division of Clinical Laboratory Science at University of North Carolina Searchable List of Clinical Laboratory Science Programs AAM Colloquium Report on Point-of-Care Testing CPEP Program Career Blog: Tips on becoming a clinical microbiology laboratory director HOM Tidbid: Papagrigorakis 2006 International Journal of Infectious Diseases report
HOM Tidbit: Shapiro reply to Papagrigorakis report
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
080: Implementing One Health with Mathew Muturi
2018/04/12
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Veterinarian and epidemiologist Mathew Muturi tells how a Rift Valley Fever outbreak led to implementation of One Health-based policies. Muturi talks about his One Health training and its applications for health and biopreparedness.
Julie’s Biggest Takeaways:
One Health
Simple communication between experts helps facilitate implementation of one health in public systems. Sitting experts in human and animal health in the same office allows easier communication between these different health sectors.
One Health policies involving close collaboration between animal and human healthcare workers were first implemented in Kenya in response to the threat of avian influenza, but were discontinued after the threat waned. Human cases of Rift Valley Fever, due to spillover from a livestock outbreak, led to the discovery that these collaborative policies could prevent other outbreaks as well, and the policies were reinstated.
Zoonotic diseases can often be the most overlooked. Officials of countries where endemic diseases are present may have preparedness plans for serious cases but may overlook something endemic like brucellosis.
There are 42 subtribes in Kenya, including diverse languages, religions, and beliefs. Public health interventions do their best to align the local beliefs of the people to minimize risk of pathogen exposure.
Featured Quotes:
“One health is not a new concept; it’s an old concept that explains the health of humans, animals, and the environment is interconnected. It’s a concept that plays out in everyday life.”
“One of the reasons One Health has been able to be successful in Kenya, and that I suggest to other countries wishing to implement this program, is the sitting together, talking together. Make sure that you work together, see each other - I don’t think communication works well enough if it’s on an ad hoc basis. The thing that has worked for us is sitting together.”
“The most important aspect of One Health is the fact that that it’s impossible to control diseases that come from animals only by focusing on humans. It’s like trying to concentrate on putting out fires without ascertaining where the fires are coming from.”
“Endemic diseases, despite the fact that they’re ever-present, are often the most ignored.”
“A lot of the risk practices are cultural, and cultural change is very slow.”
“The value of One Health is much more than the investment required to put into it. It’s one of the few things I’ve seen actually work in implementation of disease control strategies, in surveillance and in general disease control. It’s worked for Kenya and I believe it can work for all other countries.”
Links for the episode:
Republic of Kenya Zoonotic Disease Unit
Prioritization of Zoonotic Diseases in Kenya, 2015. Plos One .
079: Comparative Bacterial Genomics with Dave Rasko
2018/03/29
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Dave Rasko uses comparative bacterial genomics to find DNA sequences that influence virulence or antibiotic resistance. Dave talks about his studies of E. coli, Acinetobacter baumanii, and B. anthracis, and the state of bacterial genomics past, present, and future.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Genome sequencing speed has significantly increased: The first bacterial genome sequenced, Haemophilus influenzae, took about 10 years to complete. The first organism with two sequenced genomes was Helicobacter pylori, published in 1999, and the first organism with three published genomes was Escherichia coli. Rasko’s initial project at TIGR to sequence 11 E. coli genomes took about 2 years. Today, Rasko’s lab can sequence 500 genomes in about five days.
In E. coli, up to half of the genome can differ between two strains. The core genome is the collection of genes that will be shared among all isolates of a particular species. Core gene conservation varies among species and is important to consider in analyses for one’s species of interest.
Working on the Amerithrax investigation was unlike many other scientific inquiries for many reasons, including that the Federal Bureau of Investigation only gave the scientists involved the information pieces necessary to conduct their studies. Rasko and collaborators sequenced the genomes of spores within the samples, and found that the morphology of the colonies that grew were associated with genetic differences between the spores within the sample, linking phenotype and genotype.
While comparative genomics can provide a lot of information, there are some phenomena that will always require further study. For example, Rasko is researching isolates of A. baumanii and Klebiella pneumoniae that quickly develop drug resistance when grown in sub-inhibitory drug concentrations. The genomic sequences of resistant or susceptible strains show no difference in DNA sequence, suggesting the phenotype is due to transcriptional changes.
Featured Quotes (in order of appearance)
“Genomics is fun in that we can hypothesize all day long, every day. It’s really the start of a lot of very very hard work figuring out why.”
“There’s a lot of DNA pieces that we don’t fully understand how they moved, where they moved, where they came from. In some cases, there’s evidence to say where they came from; in terms of G-C content and coding biases, we can make some assumptions, but in the grand scheme of things, we have no idea where they’re coming from! In some cases, we’ll see them dominant throughout a lineage, and in some cases we’ll see them in sporadic isolates around the entire phylogenetic tree. . .We all thought genomics was going to solve so many problems, and it’s really just made it more difficult!”
“Plasmids tend to be mobile and exchangeable, and the pieces tend to be - I tend to think of them as legos, in the fact that you can put a plasmid together in a bunch of different ways.”
“I think a lot of conventional PCR fails and people assume that it’s because it’s negative, and not necessarily that it fails because of diversity.”
“Many microbiologists think of that colony on a plate as a clone. I force the people in my group to think about it a little differently, because it’s really what I like to call ‘genome space’. They’re not all the same; bacteria are constantly evolving. There’s changes all the time, some of them are positive, some of the are negative, the negative ones get lost, the positive ones unusually become dominant - and then there’s lots of neutral changes that just kind of hang out.”
“Genomes really normalized everything. Before that, there were certain labs that could clone and there were certain labs that could sequence, and it was a little bit restrictive to the elite labs who had those resources. Now with the genome sequences out there, everyone was starting from the same place.”
“You really have to understand your organism to make the bioinformatics work.”
Links for this episode
Rasko lab at the University of Maryland FBI summary of Amerithrax investigation 2011 PNAS report on B. anthracis comparative genomics Bugs N the ‘hood HOM Tidbit: Stanley Falkow gives both video history and written history of plasmid biology Save on Microbe 2018 , use code: asmpod
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
078: Tuberculosis treatment and mycobacterial genetics with Bill Jacobs
2018/03/15
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Bill Jacobs talks about developing mycobacterial genetic tools and using them to discover ways to shorten TB treatment. He also talks about the SEA-PHAGES program that allows high-school students to participate in phage discovery.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
The challenges of working with an easily aerosolized bacterium are aided by complementary studies on a noninfectious relative. M. smegmatus doesn’t colonize mammals and grows slower, giving researchers the opportunity to acclimate themselves to working with mycobacterial cultures.
Jacobs was the first scientist to introduce DNA into M. tuberculosis using a phasmid - part plasmid, part mycobacterial phage. The first phage came from Jacobs’ dirt yard in the Bronx, so he named it BxB1 for the Bronx Bomber. Another phage, TM4, became the workhorse phasmid when Jacobs cloned an E. coli cosmid sequence into a nonessential part of the phage genome. It replicates in E. coli as a plasmid but becomes a phage inside Mycobacteria, facilitating manipulation. The shuttle phasmids allowed transposon delivery to make transposon libraries, and the creation of gene knockouts.
To this day, we use Ziehl-Neelsen staining to differentiate acid-fast mycobacteria from gram-positive or gram-negative bacteria - the mycolic acids on the outer part of the envelope make up some of the longest microbial lipid chains. But mycobacteria can regulate its acid-fast positive or negative status; the acid-fast negative organisms are a persistent population that are often ignored inside of patients. 99.99% of M. tuberculosis bacteria are not persistent, but the last 0.1% have entered into a persistent state expressing many stress proteins that help them become refractory to killing.
A normal course of antibiotic chemotherapy for patients is six months. If infected with a strain resistant to the two frontline drugs, that time goes up to two years. The problem is even greater in extremely multidrug resistant (XDR) strains.
What we really need is a way to understand persistence and a way to shorten chemotherapy. That’s why were were absolutely amazed when we discovered that cysteine with isoniazid completely sterilizes Mtb cultures in vitro and in vivo! The culture is sterilized because the bacteria can’t form persisters. Vitamin C co-treatment with antibiotics may lead to a shortened course of therapy for TB treatment.
Neutralizing antibodies to the herpesvirus glycoprotein have been the dogma for protecting from herpes. Jacobs and his colleagues discovered that a vaccine based on a glycoprotein-knockout virus confers sterilizing immunity not through neutralizing antibodies but through antibody-dependent cell cytoxicity (ADCC). This ADCC response may also be important to develop a more effective TB vaccine.
Featured Quotes (in order of appearance):
“You’ll never know how bad your aseptic technique is until you start working with tuberculosis!”
“I think part of the reason I had the opportunity to develop genetics for TB - it’s not like it wasn’t important to do - but a lot of people were disappointed when working with the organism.”
“We’re about to take TB genetics to where yeast genetics is.”
“One of the tubicle bacilli’s greatest powers or one of its most important phenotypes is that it has the ability to persist, which means it has the ability to tolerate killing effectors, either killing by the immune system or killing by bactericidal drugs.”
“I took students to the Bronx Zoo, and over by the zebra pen, I sniffed and said ‘I smell a phage!’ In fact, that’s not crazy - anyone who plants flowers knows what good soil smells like, and in the good soil, you’re smelling the bacteria that live in the soil, the Streptomyces and Mycobacteria. I reached down and grabbed that dirt, and when we went back to work we isolated BxE1.”
“I’ve never met a phage I wasn’t excited about!”
“I now believe that most pathogens do not ‘want’ ADCC antibodies to be made, and they have immune evasion strategies where they skew the immune response to get the wrong antibodies. Since the time we published our first paper, numerous groups have shown that correlates of protection for HIV, for influenza, and for Zika, turn out to be ADCC antibodies.”
“Genetics is the mathematics of biology!”
Links for this episode
Bill Jacobs lab site NYTimes story on 1993 rapid diagnostic test using luciferase AACJournal: Vitamin C potentiates the killing of Mycobacterium tuberculosis by the first-line tuberculosis drugs isoniazid and rifampicin in mice Cell: Origins of highly mosaic mycobacteriophage genomes SEA-PHAGES program eLife: Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity mBio: Dual-reported mycobacteriophages (Φ2DRMs) reveal preexisting Mycobacterium tuberculosis persistent cells in human sputum Tuberculosis - Its cause, cure and prevention [1914] (pdf)
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
077: Influenza, politics, and scientific credibility with Ilaria Capua
2018/03/06
Ilaria Capua talks about running an internationally renowned animal influenza lab, and her time spent in the Italian Parliament. Accused of virus trafficking as part of a national scandal, she has since cleared her name and speaks here about the importance of scientific credibility and reputation.
076: Evolution of bacterial biofilm populations with Vaughn Cooper
2018/02/15
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Most bacteria live a sedentary lifestyle in community structures called biofilms. Vaughn Cooper tells us what bacterial biofilms are, why biofilms differ from test tube environments, and how long-term evolution experiments combined with population genomics are teaching us how bacteria really work. He also discusses using hands-on bacterial evolution activities to introduce high schoolers to future STEM possibilities.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Cells in a biofilm shift to dedicate their resources to protection rather than reproduction. This allows biofilms to be innately more resistant to antibiotics than those growing in planktonic culture.
One of the least-understood parts of a biofilm cycle is the dispersal stage. What cues or signals influence some biofilm-embedded cells to leave? This is a vital part of biofilm formation, since these dispersal cells can eventually attach to a new surface and restart the process of forming a biofilm.
The bead system of biofilm propagation allows Vaughn and his colleagues to study the long-term evolution of biofilms. This system, combined with population genomics, allows the study of all the different genetic changes within the population.
Traditional genetic screens compare libraries of mutants to see which survive under different conditions. Rather than on libraries of mutant strains, evolution works on random mutants that arise naturally. The accessibility of sequencing technologies has changed the way scientists study evolution, as now the mutations can be found as they form, rather than being seeded into the initial mutant library screen.
High schoolers using nonpathogenic bacteria can study evolution in action by developing new colony morphologies. Work with high schoolers and their teachers has shown students who do hands-on learning do better on standardized tests and that girls, especially, express higher interest in technology and an interest in STEM careers after a 1-2 week project.
Featured Quotes (in order of appearance)
“From a perspective of an ecologist and evolutionary biologist, this is what captivated me about biofilms: that instantly in the process of forming a biofilm, the environment becomes heterogeneous. Different cells that are clone mates are experiencing different selective pressures.”
“The hypothesis that we’ve been testing for the last 15 years or so is that biofilms in and of themselves may generate ecological and heritable evolutionary diversity in really short periods of time.”
"In describing the wrinkled Pseudomonas colonies that can stem from biofilm cells: “I think they look like hydrangeas, and some look more like doilies. I think they’re captivating and pretty charismatic as far as microbes go.”
“The average bacteria picked from any environment does an unbelieveably good job of protecting its genetic material. The per-cell mutation rate, per-genome, per-generation rate is about 1 in 1000 cells. So a bacterial cell needs to divide about 1000 times to create a single mutant. That means that mutations are actually relatively scarce, but bacterial populations are extraordinarily immense. If you grow a single cell to 108 cells, you’ve got about 105 new mutations. That’s a pretty large number. Some of them, maybe a handful, maybe 1/100 of those 105 mutations, which would be about 1000, would be beneficial. Then selection will act on them, and the better ones will rise more quickly because they make more progeny. And that’s evolution in action!”
“Increasingly, we’re using evolution to teach us about how the organism works.”
“I’m not saving lives with any of our studies on microbes in biofilm-associated infections just yet. We are seeing how they change in these infection and how they become more drug resistant. That’s great, and I think that’s a valuable contribution. But when we can encourage hundreds of high schoolers to really consider careers in the life sciences or mathematics or engineering, we’re changing lives.”
Links for this episode
Vaughn Cooper University of Pittsburgh website Rich Lenski Long-Term Evolution Experiment ASM video Journal of Bacteriology cover featuring Pseudomonas colonies Journal of Bacteriology report on the evolution of Pseudomonas biofilm diversity Journal of Bacteriology tribute to Bill Costerton Bill Costerton YouTube interview
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
075: Working with the Microbes in our Drinking and Waste Water with Marylynn Yates
2018/02/02
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Marylynn Yates discusses how the urban water cycle and its importance in eliminating waterborne pathogens. She describes the types of microbes that can survive in water and how testing for different microbial types can affect interpretation of contamination levels.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Worldwide, water is a large source of infectious disease. Billions of people have no access to safe water and this culminates in 1.5 billion cases of diarrhea and 1.5 million deaths from contaminated water annually.
The urban water cycle takes water from lakes or the ground for its first treatment before delivery to our homes. Water leaving our homes as waste water goes to a second facility where water is given a different set of treatments to eliminate disease-causing microbes before the water is returned to lakes or rivers. Different treatment facilities are needed because the concentration of contaminants is different in water before and after use in our homes.
Crystal clear spring water can be deceiving, but can carry disease-causing microbes. Animals can carry protozoans such as Giardia and Cryptosporidium, which also cause disease in people. This is why treating water, even with a simple boiling procedure, is important when backpacking or camping.
Bacterial sentinels such as Escherichia coli can be used to measure potential bacterial pathogen presence, but they don’t measure pathogenic protozoans or viruses. This is in part because the treatment necessary to eliminate bacteria is different than that necessary to eliminate protozoans and viruses. Some scientists argue that bacteriophage are a better measure of potential pathogenic virus present, though no regulations require phage monitoring. Others argue that detection of a spore-forming bacteria, such as Clostridium perfringens, would better predict protozoan presence.
Featured Quotes (in order of appearance) :
“Because there is no new water on Earth, we need to make sure that after we use water that we treat it in a way so that when it’s used again as drinking water, it’s as clean as it can possibly be.”
“Some viruses are very hardy and can survive for a long time (outside their host cell). They don’t need nutrients like bacteria do, so they just sit there - almost like a chemical contaminant.”
“Some of these viruses, such as hepatitis A virus or norovirus, can survive for a long time in the environment. When I say ‘quite a long time’, I mean for weeks or months, or in the case of hepatitis A, there was one report that it lasted up to a couple of years.”
“It’s that real-world application that has kept me going for all these years, knowing that I can have an impact on public health in my own, tiny way.”
Links for this episode
Marylynn Yates website at UCR Marylynn Yate interview with UCR mBiosphere blog post on developing water safety testing with the EPA mBiosphere blog post on developing new technologies for water safety testing Milwaukee Wisconsin Journal Sentinel 20th Anniversary of Cryptosporidiosis Outbreak Monsters Inside Me: Cryptosporidiosis
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
074: Treating Ebola in America and Fecal Transfers with Colleen Kraft
2018/01/19
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Colleen Kraft talks about treating Americans who became sick with Ebola during the west African outbreak and were evacuated to her hospital for treatment. In the second half, Kraft talks about her experience performing fecal transfers, and explains why she sees the gut microflora like a garden.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
The patient conditions couldn’t be more different between the Liberian care centers and Emory University. The nursing ratio, access to both basic and experimental medicines, and even environmental conditions such as air conditioning created drastically different healthcare experiences between the two.
While Ebola is a deadly disease, the symptoms such as headache, fever, and diarrhea are much more common than the bloody hemorrhaging often described. Patients can lose up to 10 liters of fluid each day!
Fecal microbiota transfer is a more appropriate name than transplant; new microbes overlaid on top of the dysbiotic flora will reshape the microbiota already present.
While FMT is currently used only to treat C. difficile (aka C. diff ), forthcoming studies will determine if FMT can decrease risk of an antibiotic-resistant infection by displacing resistant bacteria.
Featured Quotes(in order of appearance)
“Ebola virus disease is much more mundane than all of the novels you might read. It’s really a sepsis syndrome with a spectrum of that sepsis. Part of sepsis can be abnormal coagulation factors and low platelets, and so those bleeding complications go along with that sepsis syndrome.”
“It sounds really mundane, but supportive care is really the most important thing for these patients. When that can occur, people can recover.”
“The body doesn’t really like Ebola. One patient was encephalopathic, had kidney failure, liver failure, had some bleeding. Once the viral load was gone, all those things uprighted! It was like a capsized ship that uprighted.”
“I really view our guts like gardens. There are good fruits and vegetables when our gardens are in homeostasis. Once we use antibiotics, it kills the good fruits and vegetables of the garden and C. diff grows up like a weed. All we’re doing [when we treat C. diff ] is giving weed killer but we’re not replanting that garden.”
“I’m somebody who thinks after every antibiotic treatment for anything that we do, we should be giving people some sort of item to enrich or restore their microbiome.”
“The most exciting thing I can think of is to bring cutting-edge research and contributing to people being cured by these methods.”
Links for this episode
Colleen Kraft Emory website And the Band played on Virus Hunters of the CDC The Hot Zone NETEC Clinical Virology Symposium
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
073: Biological sex and influenza with Sabra Klein
2018/01/04
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Sabra Klein addresses the question: how does biological sex influence influenza infection and vaccination? She explains her findings on inflammation differences between males and females, and how these differences can affect the outcome of disease. Klein also discusses her advocacy for inclusion of biological sex in method reporting as a means to improve scientific rigor.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Information from the 1918 influenza pandemic suggested males died at a higher rate than females, which could be due to a gender fator or a biological factor. In 1918, men lived in close quarters of military barracks while women didn’t, representing a cultural difference of gender norms (women were exempted from military duty). But males are more susceptible to secondary bacterial infections that often accompany flu, which may represent a biological difference in infection outcome. In Klein’s studies, female mice suffer influenza more severely than males. Women who contracted the H1N1 flu epidemic in 2009 were more likely to be hospitalized with severe influenza than men. These data have yet to be aligned and leave many variables yet to explore!
Influenza infection disrupts the female menstrual cycle, causing lowered estrogen and progesterone levels. Providing exogenous progesterone can dampen inflammation and stimulate repair mechanisms needed to fix the damaged lung tissue. This type of host treatment is less likely to lead to the evolution of resistance than using antiviral compounds.
Females and males respond differently to vaccination; females mount a higher antibody response and have greater cross-protection than males.
Many diseases in addition to influenza show these sex-specific differences. The sex differences observed are specific to age; with older age, the differences are lost.
In several other countries, epidemiological and clinical data are analyzed for differences between sexes. With greater awareness, the United States may incorporate this practice too.
Featured Quotes (in order of appearance):
“Both genes as well as the hormones define the biological construct of sex.”
“There’s an ample amount of data that suggest men are less likely to wash their hands than women. We all know handwashing is probably one of the best ways to avoid contact with viruses - really anything infectious. We always have to question if we do things that influence our exposure; but in our mice studies, we can control their exposure.”
“We really have a love-hate relationship with inflammation. We need it to recognize the presence of the virus, but then we need it to dissipate. Our data suggest hormones are integral to regulating inflammation and the repair following inflammation.”
“The immune responses to the influenza vaccine - and this extends to many vaccines - are often higher in females as compared with males. This has been shown in humans as well as animal models.”
“I don’t know that I think that man flu is real. I think a lot can depend on both your age as well as your vaccine status that can influence whether you’re going to land in the hospital with severe influenza. Much like we were talking about with individuals who don’t have a vaccine, such as during a pandemic, females may be suffering a bit more, but once vaccinated females seem to do better than males. There are some nuances we shouldn’t lose sight of.”
Links for this episode
Sabra Klein website Klein speaking on heart disease differences in men and women Klein editorial in mBio: Sex reporting in microbiological and immunological research Smithsonian exhibit notification HOM Tidbit: Smithsonian article: How the horrific 1918 flu spread across America
HOM Tidbit: Aeon article: Who names diseases?
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
072: Microbial diversity of natural ecosystems with Jennifer Martiny
2017/12/20
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Jennifer Martiny describes the incredible microbial biodiversity of natural ecosystems such as soils and waterways. She explains how to add a bit of control in experiments with so many variables, and why categorizing microbial types is important for quantifying patterns.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Studying microbial community functions in their natural environment are harder to understand, but help us to parse the complexity of the natural world, in part because these experiments also include local flora and fauna that are often omitted in the controlled lab environment. Microbial cages - an actual physical barrier that contains a soil-based community - can help to disentangle the effects of the microbial community from those of the surrounding environment by adding a level of control by limiting interaction of microbes inside the nylon mesh cage with those outside of it.
Are microbial functions redundant? It depends on what function you look at - respiration is a very common function, so it’s less likely to be affected by a change in microbiome composition. Other functions, such as degrading particular compounds, may have a stronger relationship between the microbes present and those functions.
Microbes are hugely diverse! Jennifer’s comparison of all the diversity of the birds on Earth to a single bacterial taxon is mind-blowing!
Microbial categorization may be hard, but the ability to group similar organisms is necessary to formulate hypotheses and conduct experiments. It’s important to remember the groupings are manmade and sometimes have to be reconstructed!
Featured Quotes (in order of appearance)
“One of the hardest things we study is not on the microbiology side but is on the ecosystem side, measuring those biochemical functions in the environment.” (10:05)
“It’s not as if we are ever going to be able to study every particular organism out there and build a model with thousands of equations; instead what we really need to do is go after trade-offs and overall relationships that may hold across large groups, and in that way have some simple rules under different conditions like drought or temperature.” (16:45)
"Modern birds evolved about 100, 125 million years ago. Two sequences that share the 16S gene, if it’s roughly 97% identical, probably diverged 150 million years ago. That means we are lumping in all the diversity within the bacteria group within one taxon, calling it a species, which is the equivalent of lumping all birds together!" (18:47)
“It’s a bit overwhelming to imagine that for each 16S rRNA taxon, you could have as much functional, morphological, and behavioral diversity as what we see in all of birds!” (19:39)
“In biology, we’re always using an operational definition but we don’t want to get too hung up on the definition and miss all the interesting patterns going on!” (20:49)
“If you can start to quantify patterns, then you can start to ask ecological and even evolutionary questions about why we see those patterns.” (33:04)
Links for this episode
Jennifer Martiny Lab Home Page
University of California Irvine Microbiome Initiative
HOM Tidbit: TWIM 50: These things aren’t even bacteria!
Carl Woese Obituary (New York Times)
Carl Woese 1996 Feature (New York Times)
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
071: Neglected Tropical Diseases and Vaccine Advocacy with Peter Hotez
2017/12/08
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Peter Hotez talks about neglected tropical diseases: what are they, where are they found, and where did the term “neglected tropical disease” come from, anyway? Hotez discusses some of the strategies his and other groups are using for vaccine development, and his work as an advocate for childhood vaccines and global health.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Renaming “other diseases” - a large collection of disparate diseases such as schistosomiasis, leishmaniasis, and onchocerciasis (also called river blindness) - as “neglected tropical diseases” by Hotez and colleagues was integral to bringing attention to the diseases of the bottom billion, people that live on less than one U.S. Dollar per day.
Neglected tropical diseases are often chronic and debilitating without high mortality. These diseases trap people in poverty due to their long-term effects. The NTDs are often associated with terrible stigma that can lead to additional challenges for affected populations.
Neglected tropical diseases are found worldwide, in rich and poor countries. The poorest peoples living in the G20 countries (and Nigeria) now account for most of the world’s NTDs.
Parasitic infections present challenges for vaccine design, but reverse vaccinology may be a useful strategy. Reverse vaccinology mines genomes to identify promising vaccine candidates in silico , which are then narrowed sequentially for those that are expressed on the bacterial surface, immunogenic, and ultimately protective against disease. This strategy has worked for Neisseria meningitidis , and Hotez is hopeful that it will produce effective vaccines for the parasitic infections he studies.
The tradition of individual fields and departments, combined with the old-fashioned notion that scientists needn’t spend their time engaging with the public, has led to flatlined budgets and the rise of anti-science movements. Scientists need to engage the public to ensure the future of science and science-based policy.
Featured Quotes (in order of appearance):
“The concept of ‘neglected tropical diseases’ was very much born out of the Millennium Development Goals launched in the year 2000.”
“Treating NTDs in rich countries “is not a resource problem; it’s an awareness problem.”
“If you want to enter global health, we need as many people with a scientific background to go into business and law and international relations as we need to go into traditional scientific pathways”
“Many involved in the antivaccine movement disproportionately involve either parents who are affluent or educated, or both: those who know just enough to do a google search but without the background to separate the garbage from the important stuff. And of course the anti-vaccine groups are deliberately misleading.”
“Research America found that 81% of Americans can’t name a living scientist. That’s our fault. We’re so inward looking that we aren’t taking the time to do public engagement.”
Links for this episode
Peter Hotez at Baylor College of Medicine Peter Hotez website Millennium Development Goals published by the World Health Organization in 2000 WHO list of Neglected Tropical Diseases Forgotten People, Forgotten Diseases by Peter Hotez Blue Marble Health by Peter Hotez Public Health United episode featuring Hotez
HOM Tidbit: Oncocerciasis now : 1986 British Medical Journal report
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
070: Influenza vaccine and susceptibility with Stacey Schultz-Cherry
2017/11/23
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Stacey Schultz-Cherry explains the selection process to choose the influenza virus strains to include in the annual influenza vaccine. Schultz-Cherry also discusses her research on the influence of obesity on the course of disease and vaccine efficacy.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
The WHO Collaborating Centers and National Influenza Centers around the world work with a humongous network of physicians, public health workers, and veterinarians to identify strains most likely to become part of the circulating influenza viruses.
An influenza strain that makes birds very sick is not necessarily a strain that will make people sick.
Predicting phenotype from genotype remains a challenge. Receptor binding to mammalian receptors, signatures in the genome that allow it to replicate in mammalian cells, and transmission between ferrets are the marks of potentially bad strains. Genetics can also tell you a little bit about the antiviral resistance characteristics of a strain.
Why can’t we incorporate all known influenza strains into a vaccine? It’s an issue of immunodominance - having enough antibodies against an infectious agent that it will be neutralized should it cause infection. Researchers don’t know how many HAs you can incorporate to generate proper immunity to each molecular version, and this is one area of influenza vaccine research.
Obesity appears to decrease the immune response to influenza, potentially affecting the ability to form memory response. This means the vaccine is less effective, the course of disease when infected is worse, and the likelihood of secondary bacterial infection is higher.
Featured Quotes (in order of appearance)
“People don’t appreciate how much work goes into this. The importance of surveillance - if we lose our surveillance, it’s going to be very difficult to know which strains to select for the vaccine, as well as diagnostics.”
“Part of the trick is not just predicting which viral strain to use but understanding which of those strains will grow to the highest efficiency without changing when we grow it in eggs to make the vaccine.”
“My bet is, whatever we find, it’s going to end up being 10 times more complicated...which is great for my post-docs, because there’s plenty of opportunities for them to find new things and build new labs, which is ultimately the most important thing you can do as a P.I.”
“I did wound repair during my Ph.D. . . . with my background in wound repair, I said ‘what is a virus but a great big wound”
“When I was changing fields, my thesis committee asked me, ‘what are you doing? I was told it would take five years just to read the literature. You can’t change fields!’ And I said, ‘Yeah, I can.’” And I did!
“Whatever your decision is, you go for it you don’t have regrets, but you put 110% into whatever you decide to do.”
Links for this episode
Stacey Schultz-Cherry St. Jude Graduate School of Biomedical Sciences CDC Flu Activity Map HOM Tidbit: Vaccination against Influenza (review)
Send your stories about our guests and/or your comments to jwolf@asmusa.org.
069: Biopreparedness and biosecurity with Gigi Kwik Gronvall
2017/11/09
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Gigi Kwik Gronvall talks to MTM about the importance of biopreparedness. Gronvall discusses her work in creating policies around potential natural, accidental, and man-made pandemics. She describes her experiences running pandemic thought exercises that help researchers, public health workers, and governmental officials apply preparedness ideas to real-world simulations.
Host: Julie Wolf
Julie's biggest takeaways:
Thought exercises and scenarios work well for people to understand how technology, communications, human behaviors can affect the spread of infectious disease.
Many after-action reports after major biosecurity breaches, such as the Dugway contamination event, where inactivated Bacillus anthracis was accidentally shipped without being inactivated. These involve reports on what went wrong, who made mistakes, and how to prevent repeats of these errors going forward.
International groups such as the Global Health Security Alliance work with governments and institutions around the world to run dialogs and talk about biosecurity issues, safety issues, pathogen management issues. Comparing notes across countries helps to harmonize policies and find gaps that need addressing.
Bringing scientists into the policy-making meetings is the best way to write regulations in a way to protect the public, the scientists, and the research itself. Crafting good recommendations for governance prevents writing regulations that can be hard to remove.
Featured Quotes (in order of appearance) :
“There’s a public health infrastructure that’s needed to detect epidemics and respond to them appropriately. If you are lacking that infrastructure, it’s like not having a fire department anywhere close when there’s a fire. The fire gets bigger and bigger, it becomes much more difficult to be able to put out the fire, and a lot of lives are lost.”
“The thinking behind the GHSA is to boost public health infrastructure in different parts of the world that need it and to focus donor attention on some of those areas so that the weakest links are made stronger. "
“It’s going to shock no one, but it’s not always the case that the best scientific information is brought to bear on a policy issue. "
“You have to do what you can to make things a little bit harder, a little bit more challenging but still allow real, legitimate, important science to continue. Everybody sees that balance a little bit differently. "
“It’s important to me that we have someone advocating for the science and making it so it’s not onerous to be a scientist ."
“Synthetic biology changes the way we think about what biology can do. Biology has a bigger potential to be involved in industrial processes than it used to have. "
“The problem with a lot of these pathogens is that they exist in nature...you can’t take care of all options, unfortunately. "
"You can’t ever be fully prepared, but you can be in the right mindset to be surprised ."
Links for this episode
Gigi Kwik Gronvall website at Johns Hopkins University SPARS epidemic pamphlet Preparing for Bioterrorism: The Alfred P Sloan Foundation’s Leadership in Biosecurity : Book by Gronvall Synthetic Biology: Safety, Security, and Bioterrorism : Book by Gronvall
The Global Health Security Alliance homepage
Send your stories about our guests and your comments (email or recorded audio) to jwolf@asmusa.org.
068: Microbiomes everywhere with Jack Gilbert
2017/10/25
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Jack Gilbert talks about his studies on microbiomes of all sorts. He describes the origin of the Earth Microbiome Project, which has ambitions to characterize all microbial life on the planet, and talks more specifically about the built microbiome of manmade ecosystems such as hospitals. Gilbert explains how advances in scientific techniques have driven past microbiome-related discoveries and will continue to do so in the future.
Host: Julie Wolf
Subscribe (free) on iPhone , Android , RSS , or by email . You can also listen on your mobile device with the ASM Podcast app .
Julie's biggest takeaways:
Insect-pathogenic fungi living in plant roots can pass nitrogen from killed insects to their plant hosts, receiving different carbon nutrients from the plants in return.
Fungi harvested after growth on inexpensive materials like chicken droppings are used in agriculture both as fertilizer and as insecticide.
Cyclosporine was first discovered in insect-pathogenic fungi.
Raymond St. Leger and other scientists working to introduce genetically modified microbes into the environment deeply consider the societal effects of their work, including collaboration with local communities, governmental regulatory bodies, and trusted leaders and tailor their efforts to the regional area.
Featured Quotes (in order of appearance):
“We really can apply ecological understanding of microbiomes and microbial ecosystems to any environment.”
“I think basic research is absolutely essential but I always want to think about what that could lead to in the future.”
“Reproducibility is key and extraordinarily difficult in all fields of science due to lack of appropriate funding and a zeitgeist in science that discourages scientists from reproducing one another’s studies.”
“We are forever striving to validate the predictions we derive from our descriptive work. We create SO MANY predictions!”
“No small dreams, no small goals - go big or go home! At the end of the day, we all want to feel like we’re doing something that makes an impact.”
“I love to collaborate. I love to work with other people, brilliant people in the microbiome field”
“I’m often accused of not being focused enough. What does Jack Gilbert do? Well, I do a little bit of everything - as long as there’s a microbe involved! I like it like that; it keeps me energized.”
Links for this episode
Jack Gilbert website at University of Chicago Jack Gilbert TedxNaperville Talk Earth Microbiome Project home page Dirt is Good - new book by Gilbert and Rob Knight History of Microbiology Tidbit: Joshua Lederberg piece in The Scientist on ‘microbiome’ nomenclature in 2001.
Send your stories about our guests and your comments (email or recorded audio) to jwolf@asmusa.org.
067: MRSA in agriculture and zombie epidemiology with Tara C. Smith
2017/10/12
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Tara C. Smith discusses her work uncovering ties between agriculture and methicillin-resistant Staphylococcus aureus (MRSA). Her studies have found MRSA on and around pig farms, on animal handlers, and even in packaged meat in the grocery store. She also talks about using zombies as an allegory for infectious disease outbreak preparedness.
Links for this episode
Tara C. Smith website
Aetiology Blog on Science Blogs Network
Outbreak News Interview with Smith on her work communicating the science around vaccines and fighting anti-vaccine sentiments.
Smith’s collected writings on Ebola and emerging infectious diseases
Zombie Infections: Epidemiology, Treatment, and Prevention in the British Medical Journal
History of Microbiology tidbit: Thomas Jukes’ 1968 Letter to the British Medical Journal and 1997 Recollections in Protein Science .
Julie’s biggest takeaways:
MRSA transitioned from primarily hospital-acquired to community-acquired infections in the 1990s. In the early 2000s, MRSA strains associated with livestock farming emerged in Europe. Smith’s group was the first to identify agriculture-associated MRSA strains in the United States.
Tara found MRSA on the very first farm in which she and her colleagues looked for MRSA.
The MRSA strain ST398 appears to have originated in people as MSSA then moved to livestock, where the strain acquired some antibiotic resistance related genes. This is because zoonotic diseases are a two-way street and microbes can pass from people to animals, as well as passed from animals to people.
Many factors may contribute to MRSA contamination of consumer meat products: for one, MRSA in farms is aerosolized and the same may be true in meat processing facilities. People can also be colonized and spread from workers to products. It’s likely a mixture of strains from farms and strains from people working in the packing plants.
Farms that raise animals without antibiotics were not positive for MRSA. Processing these animals at plants where conventional animals are raised creates potential for cross-contamination, however.
Prophylactic and treatment applications of antibiotics are still allowed for livestock, but antibiotics used for growth promotion purposes were phased out in January 2017.
Featured quotes:
“I was in Iowa, the #1 pig-producing state. We started looking for MRSA + found them on the very 1st farm we sampled”
“When we think of zoonotic diseases, usually we think of microbes that come from animals to people, but there can be bidirectional transmission. It’s definitely not just a one-way street
“That it doesn’t cause disease in pigs made S. aureus invisible to people studying its epidemiology for quite a while”
“Our biohazard people probably hated us because we had pounds and pounds of meat products we were checking” for MRSA
"S. aureus is definitely not the only one - there’s lots of bacteria that are affected by use of antibiotics on farms”
“Everything zombies now is a virus!”
066: Insect-pathogenic fungi as fertilizers and mosquito control with Raymond St. Leger
2017/09/28
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Raymond St. Leger describes his work on insect pathogenic fungi. Members of this diverse group of fungi can be found as part of the plant rhizosphere, where they provide nutrients to the plant, and can also be deployed as insect control agents. Raymond discusses his work with communities in Burkina Faso, where he works with officials to educate and gain consent for use of mosquito-killing fungi to control the spread of malaria.
Host: Julie Wolf
Subscribe (free) on iPhone, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app .
Julie's biggest takeaways:
Insect-pathogenic fungi living in plant roots can pass nitrogen from killed insects to their plant hosts, receiving different carbon nutrients from the plants in return.
Fungi harvested after growth on inexpensive materials like chicken droppings are used in agriculture both as fertilizer and as insecticide.
Cyclosporine was first discovered in insect-pathogenic fungi.
Raymond St. Leger and other scientists working to introduce genetically modified microbes into the environment deeply consider the societal effects of their work, including collaboration with local communities, governmental regulatory bodies, and trusted leaders and tailor their efforts to the regional area.
Featured Quotes:
"Possibly fungi kill more organisms than any other disease-causing agents." (2:55)
"People are interested in how you can utilize a plant-root colonizing Metarhizium as a comprehensive biofertilizer." (14:30)
"Put elite Metarhizium onto corn seeds and you can boost the growth of corn by about 30%." (14:50)
"Mosquitos and malaria have no friends." (23:17)
"If an insect is especially common, then a strain of Metarhizium will specialize to that insect." (24:35)
“There’s a lot of different ethical, political, and social concerns we have to address and we have to resolve before any type of genetically manipulated product can be introduced. We even have questions about the meaning of informed consent!" (28: 30)
"Synbio-phobia-phobia: the belief that genetic engineers have that people are going to be frightened of their work."(32:00)
"In Burkina Faso, you can expect to get more than 200 bites from Anopholes gambiae a day. This is malaria central." (37:58)
Links for this episode
Raymond St. Leger website at the University of Maryland St. Leger lab research explained in a three-minute video NPR story covering fungal pesticides as alternatives to chemicals
Discover Magazine blog on malaria-fighting Frankenfungus CHOMA tidbit: Felix d'Herelle and the Origins of Molecular Biology by Bill Summers (Excerpt of Chapter 3. Epizootics: Locusts in Argentina and Algeria ).
Send your stories about our guests and/or your comments (email or recorded audio) to jwolf@asmusa.org .
065: Polio Research Breakthroughs with Vincent Racaniello
2017/09/28
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Vincent Racaniello discusses how he ended up studying polio virus and the three eureka moments he’s experienced so far: uncovering the polio genome, discovering the polio receptor, and generating a mouse model of polio disease. Vincent discusses his interest in science communications, including his blog and active podcast network.
Host: Julie Wolf
Activities of the National Foundation for Infantile Paralysis in the Field of Virus Research (free) on iPhone, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app .
Julie's biggest takeaways:
All three polio virus serotypes are covered by the polio vaccine; type 2 has been eradicated and type 3 is close to being eradicated. Enterovirus 68 is a related enteroviruses that is associated with paralysis, but its receptor and disease progression remain largely unknown. Developing tools and techniques to study one virus that can cross into the central nervous system, such as polio, can set up a lab to study other neurotropic viruses, such as enterovirus 68 and Zika virus. All scientists with access to a computer and a social media account can be effective science communicators!
Featured Quotes:
"You have to find people to be mentors who you are going to listen to, and if they give you advice, you follow it." (6:57)
"It took me one year to sequence the genome of polio, which you could do in five minutes today." (9:52)
"We work on infectious agents and a big part of it is to eradicate them and alleviate human disease." (20:32)
"On facebook, you’ve lots of friends who are following you; if you show them science, some of them will listen to it." (33:30)
"We all have to share what we do. We’re funded mostly by tax dollars, and we have to let the public know what we do." (34:00)
Links for this episode
Vincent Racaniello Zika Diaries : a blog about the Racaniello lab experiences studying Zika Virus Virology Blog This Week in Virology Scientists: Engage the Public! CHOMA tidbit: Activities of the National Foundation for Infantile Paralysis in the Field of Virus Research by Paul de Kruif
Send your stories about our guests and/or your comments (email or recorded audio) to jwolf@asmusa.org .
Welcome to Meet the Microbiologist!
2017/09/24
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Welcome back, Meet the Scientist subscribers! For those of you who never heard an episode of Meet the Scientist, thanks for taking a listen. We're excited to tell all of you we're now Meet the Microbiologist (MTM). MTM is the same great, one-on-one conversations captured in Meet the Scientist just with a new name and a new host.
Julie Wolf of the American Society for Microbiology will be bringing back the podcast with all new episodes with scientists who work in one of the many areas of the microbial sciences — genomics, antibiotic resistance, virology, synthetic biology, emerging infectious diseases, microbial ecology, public health, probiotics, and more!
The first two new episodes will be released September 28th, beginning with an episode with Vincent Racaneillo of This Week in Microbiology taking about his research on polio and Zika virus, and his experience as a science communicator. The other episode, released the same day, is with Raymond St. James discussing applications of insect-pathogenic fungi as plant fertilizers and mosquito control agents.
Make sure to subscribe, for free, wherever you listen to podcasts including iTunes , Android , or get each episode delivered by email . Subscribing to the podcast is the best way to make sure you never miss an episode!
Talk to you soon!
MTS64 - Martin Blaser - Save Our Endangered Germs
2010/12/29
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In this podcast, I speak to Martin Blaser, Frederick H. King Professor of Internal Medicine and Chairman of the Department of Medicine and Professor of Microbiology at the New York School of Medicine. Blaser studies Helicobacter pylori, bacteria that live in the stomachs of billions of people. Blaser has shown that H. pylori has a strange double life inside of us. On the one hand, it can cause ulcers and gastric cancer. On the other hand, it can protect us from diseases of the esophagus, allergies, asthma, and perhaps even obesity. We're now eradicating H. pylori with antibiotics and other luxuries of modern life; Blaser thinks we ought to bring it back--but keep it on a tight leash.
MTS63 - Jeff Gralnick - I Sing the Microbe Electric
2010/12/16
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All life hums with electricity, from our heartbeats to the electrons that flow to the oxygen we breathe.But some bacteria are electricians par excellence, generating electric currents in the soil and water.
In this podcast, I talk to microbe-electricity expert Jeff Gralnick of the University of Minnesota about the biology behind these currents, and how engineers may be able to harness it to power technology.
MTS62 - Jessica Green - The Living Air
2010/11/23
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In this podcast I talk to Jessica Green of the University of Oregon about aerobiology: the science of life in the air.
We live in an invisible ocean of life, with millions of microbes swarming around us. Microbes can live many miles high in the upper atmosphere, and they may actually be able to feed and grow in clouds. Green and I talk not just about high-altitude aerobiology, but about the microbes we share our homes and offices with, and how better understanding them can help our health.
MTS61 - Charles Bamforth - Beer: Eight thousand years of biotechnology (39.5 min.)
2010/11/04
In this podcast, I talk to Charles Bamforth of the University of California, Davis, about the surprisingly complex chemistry of beer, and the pivotal role microbes play in making it happen.
MTS60 - Thomas Scott - The Bone-Breaking Virus (29.5 min.)
2010/10/20
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In this podcast I talk to Thomas Scott of the University of California, Davis, about dengue fever, a disease that's on the rise. Spread by mosquitoes, it can make you feel as if your bones are broken and leave you exhausted for months. In more serious cases, people suffer uncontrollable bleeding and sometimes die. Dengue is expanding its range, and is even making incursions into the United States. Scott and I talk about what scientists know and don't know yet about dengue, and what the best strategy will be to drive the virus down.
MTS59 - Charles Ofria - Digital Life
2010/10/06
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In this podcast I talk to Charles Ofria , a computer scientist at Michigan State University.
Ofria and his colleagues have created a program called Avida in which digital organisms can multiply and evolve. They are studying many of evolution's deepest questions, such as how complexity evolves from simplicity and why individuals make sacrifices for each other. The evolution unfolding in Avida is also yielded new software that can run robots and sensors in the real world.
Bonus Content includes:
Avida Movie
In this movie, we started with a normal Avida organism in the middle of the population and let it grow for a while before injecting a highly-virulent parasite into the middle. The hosts are all colored with shades of blue and the parasites are shades of red.
MTS58 - David Baker - Crowdsourcing Biology
2010/09/23
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In this podcast I spoke to David Baker , a professor of biochemistry at the University of Washington. Baker and his colleagues study how proteins fold, taking on the complex shapes that make our lives possible.
It turns out that protein folding is a fiendishly hard problem to solve, and even the most sophisticated computers do a poor job of solving it. So Baker and his colleagues have enlisted tens of thousands of people to play a protein-folding game called Foldit . I talked to David Baker about the discoveries they've made through crowdsourcing, and the challenges of getting 57,000 co-authors listed on a paper.
Additional Resources:
Rosetta@Home
Foldit
MTS57 - Forest Rohwer - Curing the Corals
2010/09/01
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It never occurred to me that the human body and a coral reef have a lot in common--until I spoke to Forest Rohwer for this podcast. Rohwer is a microbiologist at San Diego State University, and he studies how microbes make coral reefs both healthy and sick. Just as we are home to a vast number of microbes, coral reefs depend on their own invisible menagerie of algae and bacteria to get food, recycle waste, and fend off invaders. But as Rohwer writes in his new book, Coral Reefs in the Microbial Seas, we humans have thrown this delicate balance out of kilter, driving the spread of coral-killing microbes instead.
Additional Reading:
Viral communities associated with healthy and bleaching corals.
The lagoon at Caroline/Millennium atoll, Republic of Kiribati: natural history of a nearly pristine ecosystem.
Metagenomic analysis of stressed coral holobionts.
MTS56 - Susan Golden - Clocks for Life
2010/08/18
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In this podcast, I talk to Susan Golden , the co-director of the Center for Chronobiology at the University of California at San Diego.
We talked about Golden's research into time--in particular, how living things know what time it is. While you may have heard of our own "body clock" that tracks the 24-hour cycle of the day, it turns out that some bacteria can tell time, too. Golden has discovered how evolution has produced a molecular clock inside microbes far more elegant than any manmade timepiece.
Additional Reading:
Proteins Found in a CikA Interaction Assay Link the Circadian Clock, Metabolism, and Cell Division in Synechococcus elongatus
Quinone sensign by the circadian input kinase of the cyanobacterial circadian clock
MTS55 - Nancy Moran - The Incredible Shrinking Microbe
2010/08/04
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How many genes can a species lose and still stay alive? It turns out, bacteria can lose just about all of them!
In this podcast, I talk to Nancy Moran of Yale University about her fascinating work on the microbes that live inside insects such as aphids and cicadas. After millions of years, they have become stripped down creatures that are revealing some profound lessons about how superfluous most genes are--at least if you live inside a host.
Recent Publications:
Bacterial genes in the aphid genome: absence of functional gene transfer from Buchnera to its host
Symbiosis and insect diversification: an ancient symbiont of sap-feeding insects from the bacterial phylum Bacteroidetes
MTS54 - Carl Bergstrom - The Mathematics of Microbes
2010/07/14
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In this podcast I talk to Carl Bergstrom of the University of Washington about the mathematics of microbes.
Bergstrom is a mathematical biologist who probes the abstract nature of life itself. We talk about how life uses information, and how information can evolve. But in Bergstrom's hands, these abstractions shed light on very real concerns in medicine, from the way that viruses jam our immune system's communication systems to to the best ways to fight antibiotic resistance.
Publications:
Mapping Change in Large Networks [html] [pdf]
The transmission sense of information [pdf]
Dealing with deception in biology [pdf]
MTS53 - Bonnie Bassler - The Bacterial Wiretap
2010/07/01
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In this podcast I talk to Bonnie Bassler , a professor at Princeton and the president-elect of the American Society for Microbiology.
Bassler studies the conversations that bacteria have, using chemicals instead of words, Her research is not only helping to reveal how bacteria work together to make us sick, but also how we might interrupt their dialogue in order to cure infections.
Related Projects:
Measurement of the copy number of the master quorum-sensing regulator of a bacterial cell.
Information processing and signal integration in bacterial quorum sensing.
MTS52 - Mitchell Sogin - Expeditions to the Rare Biosphere
2010/06/17
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In this podcast, I talk to Mitchell Sogin , the Director of the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution at the Marine Biological Laboratory in Wood's Hole, Massachusetts.
Dr. Sogin is one of the leaders of an ambitious project to survey the microbes of the ocean--which total over 36,000,000,000,000,000,000,000,000,000,000 cells. Using the latest DNA-sequencing technology, D r. Sogin and his colleagues are cataloging microbes from all over the world, and are discovering a genetic diversity in the microbial world far exceeding anyone's expectations.
Dr. Sogin explained how most species they find only exist in small numbers, while a minority of species dominate their samples. Dr. Sogin is investigating how this "rare biosphere" changes the way we understand how the ocean's ecosystems work.
Related Projects:
International Census of Marine Microbes
Woods Hole Center for Oceans and Human Health
MTS51- James Liao - Turning Microbes into Fuel Refineries
2010/06/02
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In this podcast I talk to James Liao , a professor in the Department of Chemical and Biomolecular Engineering at UCLA. I spoke to Dr. Liao about his research into engineering microbes to make fuel.
Today, we get most of the fuel for our cars out of the ground. It's a process fraught with dangerous consequences, from the oil spill in the Gulf of Mexico to the rise in global temperatures thanks to greenhouse gases. Dr. Liao is among a growing number of scientists who think that microbes can help us out of this predicament.
We talked about the attraction of microbe-derived fuels, and the challenges of getting bacteria to turn air, water, and sun into something that can power your car.
Selected Publications
Atsumi, S.; T. Hanai and J.C. Liao (2008) Non-Fermentative Pathways for Synthesis of Branched-Chain Higher Alcohols as Biofuels, Nature , 451:86-89.
Atsumi,S.; Higashide, W.; and Liao, J.C. (2009) Direct recycling of carbon dioxide to isobutyraldehyde using photosynthesis, Nat Biotechnol , 27, 1177-1180
MTS50.5 - The Making of the Meet the Scientist Podcast
2010/05/21
To mark the celebration of Microbeworld's 50th episode of the Meet the Scientist podcast, we created a time lapse video that shows exactly what it takes to produce a single episode of the show.
We hope you enjoy this behind the scenes look and we thank you for listening week after week. Cheers, to another 50 episodes!
MTS50 - R. Ford Denison - Darwin on the Farm
2010/05/19
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In this podcast, I talk to R. Ford Denison of the University of Minnesota. Denison is an evolutionary biologist who's interested in how to make agriculture better. The ways in which plants thrive or fail are shaped by their evolutionary history, as well as the evolution that unfolds every planting season.
We're most familiar with the evolution of resistance to pesticides in insects and to herbicides in weeds. But evolution has many other effects on farms. For example, many important crop plants, like soybeans, cannot extract nitrogen from the atmosphere on their own. They depend instead on bacteria that live inside their roots.
In exchange for fixed nitrogen, the bacteria get nutrients from the plants. It may seem like a happy case of cooperation, but the evolution of cooperation always runs the risk of cheating and deception. How plants and bacteria come to a compromise is a remarkable story that Denison and his colleagues are now documenting.
Selected Publications
Denison, R.F. 2010. Darwinian agriculture: where does nature's wisdom lie? Book in preparation for Princeton University Press.
Ratcliff, W.C., P. Hawthorne, M. Travisano, R.F. Denison. 2009. When stress predicts a shrinking gene pool, trading early reproduction for longevity can increase fitness, even with lower fecundity . PLoS One 4:e6055
Kiers E. T., R.A. Rousseau, S. A. West, and R. F. Denison. 2003. Host sanctions and the legume-rhizobium mutualism . Nature 425:78-81.
MTS49 - Irwin Sherman - The Quest for a Malaria Vaccine: The First Hundred Years
2010/05/05
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In this podcast, I talk with Irwin Sherman, professor emeritus at the University of California at Riverside, about the century-long quest for a vaccine against malaria.
Scientists have been trying to make a vaccine for the disease almost since the discovery of the parasite that causes malaria. Yet decade after decade, they've encountered setbacks and failures. We talked about why it's so hard to make a malaria vaccine, and how likely it is that scientists will ever be able to do so in the future.
If you want to find out more about this long-running saga, check out Sherman's new book, The Elusive Malaria Vaccine: Miracle or Mirage .
About the Book
Chronicling a 100-year quest, this book tells the fascinating story of the hunt for the still-elusive malaria vaccine. Its clear, engaging style makes the book accessible to a general audience and brings to life all the drama of the hunt, celebrating the triumphs and documenting the failures. The author captures the controversies, missteps, wars of words, stolen ideas, and clashes of ego as researchers around the world compete to develop the first successful malaria vaccine.
The Elusive Malaria Vaccine: Miracle or Mirage? is based on author Irwin W. Sherman’s thorough investigation of the scientific literature as well as his first-hand interviews with today’s pioneers in malaria vaccine research. As a result, the book offers remarkable insights into the keys to a successful malaria vaccine and the obstacles hindering its development.
Malaria is one of humankind’s greatest killers, currently afflicting some 300 to 500 million people. Moreover, malaria infections have begun to spread and surge in places previously free from the disease. With the book’s easy-to-follow coverage of such topics as immunity, immunology, recombinant DNA, and monoclonal antibodies, readers gain a new understanding of the disease itself, the importance of microbe hunters, and the need for responsible leadership to face the challenges that lie ahead in the battle against malaria.
Other Publications from Dr. Sherman
Twelve Diseases That Changed Our World
The Power of Plagues
MTS48 - Keith Klugman - Pneumonia: The Hidden Giant
2010/04/21
MTS47 - Peter Daszak - Stalking the Wild Microbe
2010/04/07
MTS46 - Curtis Suttle - It's a Virus World and We Just Live On It
2010/03/24
MTS45 - James Collins - Engineering Life: The Past and Future of Synthetic Biology
2010/03/04
MTS44 - Michael Worobey - In Search of the Origin of HIV and H1N1's Hidden History
2010/02/18
MTS43 - Rob Knight - The Microbes That Inhabit Us
2010/02/03
MTS42 - Julian Davies - The Mysteries of Medicine's Silver Bullet
2010/01/20
MTS41 - Sallie Chisholm - Harvesting the Sun
2010/01/06
MTS40 - John Wooley - Exploring the Protein Universe
2009/12/23
MTS39 - Paul Turner - Pandemic in a Petri Dish
2009/12/07
MTS38 - Jonathan Eisen - An Embarrassment of Genomes
2009/11/05
MTS37 - Hazel Barton - Cave Dwellers
2009/10/23
MTS36 - Dennis Bray - Living Computers
2009/10/09
MTS35 - Michael Cunliffe - The Ocean's Living Skin
2009/09/11
MTS34 - Pratik Shah - Combatting Pathogens with Polyamines
2009/08/28
MTS33 - Abigail Salyers - The Art of Teaching Science
2009/08/13
MTS32 - Arthur Guruswamy - Mycobacterial and Fungal Pathogens
2009/07/29
MTS31 - Frances Arnold - Engineering Microbes
2009/07/15
MTS30 - Stanley Plotkin - The Past, Present, and Future of Vaccines
2009/07/01
MTS29 - Christine Biron - The Innate Immune System
2009/06/18
MTS28 - Joseph DeRisi - New Tech Approaches to Infectious Disease
2009/06/02
MTS27 - Melanie Cushion - Pneumocystis carinii
2009/05/14
MTS26 - Ian Orme - Tuberculosis
2009/05/07
MTS25 - Parisa Ariya - Bioaerosols | The Living Atmosphere
2009/04/23
MTS24 - Jeff Bender - MRSA in Animals
2009/04/17
MTS23 - Jo Handelsman - The Science of Bug Guts
2009/04/10
MTS22 - David Knipe - Herpes Simplex Virus 2 (HSV-2)
2009/03/31
MTS21 - Andrew Knoll - Ancient Life and Evolution
2009/03/17
MTS20 - Roberto Kolter - Bacillus Subtilis and Bacteria as Multicellular Organisms
2009/03/12
MTS19 - Ellen Jo Baron - The Challenges and Rewards of Working in the Developing World
2009/03/05
MTS18 - Elizabeth Edwards - Cleaning Up Solvents in Groundwater
2009/02/25
MTS17 - Stuart Levy, MD - Antibiotic Resistance and Biosecurity
2009/02/12
MTS16 - Paul Keim, Ph.D. - The Science Behind the 2001 Anthrax Letter Attacks
2009/02/02
MTS15 - Kathryn Boor - The Science of Foodborne Pathogens
2009/01/21
MTS14 - Moselio Schaechter - Successful Science Blogging and Hunting Mushrooms
2009/01/07
MTS13 - Video Supplement - Proteopedia Video Guide
2008/12/31
MTS13 - Joel Sussman - Proteopedia.org and Intrinsically Unstructured Proteins
2008/12/31
MTS12 - Nancy Keller - Aspergillus and the Fungal Toxin Problem
2008/12/23
MTS11 - Daniel Lew - The Yeast Cell Cycle
2008/12/08
MTS10 - Anthony Maurelli - Black Holes and Antivirulence Genes
2008/11/25
MTS9 - Stanley Falkow - 21st Century Microbe Hunter
2008/11/21
MTS8 - Rachel Whitaker - The Evolution of Sulfolobus
2008/11/14
MTS7 - Anthony Fauci - Managing Infectious Disease on a Global Scale
2008/11/11
MTS6 Bruce Rittmann - Microbes, Waste and Renewable Energy
2008/10/09
MTS5 Brett Finlay - E.coli and the Human Gut
2008/10/02
MTS4 David Relman - The Human Microbiome
2008/09/25
MTS3 Ute Hentschel - Symbiotic Sea Sponges
2008/09/19
MTS2 - Seth Darst - RNA polymerase
2008/09/09
MTS1 Ralph Tanner - The Future of Biofuels
2008/08/18
Meet the Microbiologist
https://www.asm.org/mtm
Who is microbiology? Meet the Microbiologist (MTM) introduces you to the people who discover, innovate and advance the field of microbiology.
Go behind-the-scenes of the microbial sciences with experts in virology, bacteriology, mycology, parasitology and more! Share in their passion for microbes and hear about research successes and even a few setbacks in their field.
MTM covers everything from genomics, antibiotic resistance, synthetic biology, emerging infectious diseases, microbial ecology, public health, social equity, host-microbe biology, drug discovery, artificial intelligence, the microbiome and more!
From graduate students to working clinicians and emeritus professors, host, Ashley Hagen, Scientific and Digital Editor at the American Society for Microbiology, highlights professionals in all stages of their careers, gleaning wisdom, career advice and even a bit of mentorship along the way.
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