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Explore every episode of the podcast Meet the Microbiologist

Dive into the complete episode list for Meet the Microbiologist. Each episode is cataloged with detailed descriptions, making it easy to find and explore specific topics. Keep track of all episodes from your favorite podcast and never miss a moment of insightful content.

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TitlePub. DateDuration
When Proteins Become Infectious: Understanding Prion Disease With Neil Mabbott23 Aug 202400:55:53

From Bovine Spongiform Encephalopathy (BSE) to Creutzfeldt-Jakob disease (CJD), Neil Mabbott, Ph.D., has worked for nearly 2 decades on understanding the mechanisms by which prion proteins become infectious and cause neurological disease in humans and animals. He discusses the remarkable properties of prions and addresses complexities surrounding symptoms, transmission and diagnosis of prion disease.

Trillion Dollar Microbes Make the Bioeconomy Go Round With Tim Donohue28 May 202400:49:03
Episode Summary Timothy Donohue, Ph.D.—ASM Past President, University of Wisconsin Foundation Fetzer Professor of Bacteriologyand Director of the Great Lakes Bioenergy Research Center (GLBRC) calls genomics a game-changer when it comes the potential of microbes to create renewable resources and products that can sustain the environment, economy and supply chain around the world. He also shares some exciting new advances in the field and discusses ways his research team is using microorganisms as nanofactories to degrade lignocellulose and make a smorgasbord of products with high economic value.

Take the MTM listener survey! Ashley's Biggest Takeaways:
  • The bioeconomy can be broadly defined as the use of renewable resources, including microorganisms, to produce valuable goods, products and services.
  • Microbes have the potential to create products that cannot be made by existing synthetic chemistry routes.
  • Using raw, renewable resources to create a circular bioeconomy is beneficial to the environmental footprint, economic footprint and supply chain security around the globe.
Links for This Episode:
Microbial Flavor Profiles for Bread and Wine Production With Kate Howell14 Jul 202300:37:38
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:


Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.

MTS60 - Thomas Scott - The Bone-Breaking Virus (29.5 min.)20 Oct 201000:29:44

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 Life06 Oct 201000:45:19

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 Biology23 Sep 201000:24:26

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 Corals01 Sep 201000:23:52

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.

AncientBiotics With Steve Diggle and Freya Harrison02 Jun 202300:42:26

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.


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 Lee05 May 202300:34:00
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:

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 Blaser13 Apr 202300:49:06

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 Self-Experimentation of Barry Marshall07 Feb 202300:56:31

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 Fauci22 Dec 202201:13:03

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.

MTS8 - Rachel Whitaker - The Evolution of Sulfolobus14 Nov 200800:17:23

Rachel Whitaker is an assistant professor of microbiology at the University of Illinois at Urbana-Champaign, where she has developed a research program focused on the evolutionary ecology of microorganisms. Much of Dr. Whitaker’s work centers around a hyperthermophile found in geothermal springs: the archaeon Sulfolobus islandicus.

Evolution is not just history – it’s still in action today, molding humans, plants, animals and, of course, microbes, in ways we still don’t completely understand. One of Whitaker’s focus areas is archaea, a group of single-celled microbes that are found in some of the harshest environments on earth. By looking at how one variety of archaea, Sulfolobus, varies from place to place, Whitaker hopes to find whether Sulfolobus is adapting new characteristics to suit its habitats, and whether this kind of adaptation can help us explain why there are so many different kinds of microbes in the world.

In this interview, I asked Dr. Whitaker about the hot springs where she studies Sulfolobus, whether it’s hard to communicate with ecologists who work with bigger organisms, and about new discoveries she’s made related to an immune system in archaea.

MTS7 - Anthony Fauci - Managing Infectious Disease on a Global Scale11 Nov 200800:15:23

Dr. Anthony Fauci is the director of NIAID – the National Institutes for Allergy and Infectious Disease – where he is also Chief of the Laboratory of Immunoregulation. Dr. Fauci’s research interests lie primarily in the molecular mechanisms of HIV and AIDS, and he has published extensively on the interactions of HIV with the immune system. He’ll be speaking at the opening session of ICAAC – the Interscience Conference on Antimicrobial Agents and Chemotherapy – on October 25 in Washington DC, where he’ll describe some of the remaining challenges in the fight against HIV, tuberculosis, and antibiotic resistant microbes.

Dr. Fauci is not only a researcher, he is also an important player in science policy in the U.S. He was a primary architect of PEPFAR, the President’s Emergency Plan for AIDS Relief, a program that received reauthorization and has a budget of $48 billion for HIV/AIDS, tuberculosis, and malaria around the world. In honor of his efforts to improve our understanding and treatment of HIV and AIDS, Dr. Fauci was recently awarded the Presidential Medal of Freedom, the nation’s highest civil award.

In this interview, I talked with Dr. Fauci about progress in managing infectious disease on a global scale, why it’s the “devil you don’t know” that is still the scariest infectious disease of all, and about the roles of abstinence education and condom awareness in PEPFAR.

Françoise Barré-Sinoussi's Discovery of HIV19 Nov 202200:57:55
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 Drown28 Oct 202200:38:23
Episode Summary 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 Booss17 Oct 202200:55:21
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 Shieh01 Oct 202201:11:44

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.

Rabies: The Diabolical Virus With Many Symptoms and Hosts With Rodney Rohde07 May 202400:55:20

Rodney Rohde, Ph.D., Regents' Professor and Chair of the Medical Laboratory Science Program at Texas State University discusses the many variants, mammalian hosts and diverse neurological symptoms of rabies virus.

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Ashley's Biggest Takeaways:
  • Prior to his academic career, Rohde spent a decade as a public health microbiologist and molecular epidemiologist with the Texas Department of State Health Services Bureau of Laboratories and Zoonosis Control Division, and over 30 years researching rabies virus.
  • While at the Department of Health Lab, Rohde worked on virus isolation using what he described as "old school" cell culture techniques, including immunoassays and hemagglutinin inhibition assays.
  • He also identified different variants of rabies virus, using molecular biology techniques.
  • Rohde spent time in the field shepherding oral vaccination programs that, according to passive surveillance methods have completely eliminated canine rabies in Texas.
  • In the last 30-40 years, most rabies deaths in the U.S. have been caused by bats.
  • Approximately 98% of the time rabies is transmitted through the saliva via a bite from a rabid animal.
  • Post-exposure vaccination must take place before symptoms develop in order to be protective.
Links for This Episode:
Lyme Disease Prevention and Treatment with Linden Hu02 Sep 202200:31:49
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:
Tardigrades and Microbial Midwives with Mark O. Martin08 Aug 202200:54:01

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:

Shark Epidermis Microbiome with Elizabeth Dinsdale20 May 202200:43:22

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:

Microbial Culture Collections and the Soil Microbiome with Mallory Choudoir18 Apr 202200:43:43

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 Hotez01 Nov 202100:45:39

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 Colwell10 Jun 202100:47:49

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 Akob12 Nov 202000:43:56

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:

 

131: Powassan virus and tick biology with Marshall Bloom31 Jul 202001:02:06

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:

130: Bioremediation of oil spills with Joel Kostka19 May 202000:49:32
129: Arbovirus evolution with Greg Ebel23 Apr 202000:54:25

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: 

 

 

Increasing Laboratory Capacity for TB Diagnosis With Aureliana Chambal09 Mar 202400:35:20

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:
128: Managing Plant Pathogens Using Streptomyces with Linda Kinkel26 Mar 202001:03:01

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.

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127: E. coli and Burkholderia vaccines with Alfredo Torres02 Mar 202000:55:11

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:

  1. 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. 

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126: Placental biology, infection and immunity with Carolyn Coyne14 Feb 202000:59:45

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.

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125: Coronavirus Antiviral Drug Discovery with Timothy Sheahan31 Jan 202000:52:37

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.

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124: Gastroenteritis Viruses with Mary Estes10 Jan 202000:54:35

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.

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123: SAR11 and Other Marine Microbes with Steve Giovannoni21 Dec 201900:55:18

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.

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122: Prions and Chronic Wasting Disease with Jason Bartz06 Dec 201900:49:38
121: Microbial Interkingdom Interactions with Deb Hogan21 Nov 201900:54:12

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.

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Bonus: Diagnosing C. diff Infections for Optimal Patient Outcomes with Colleen Kraft18 Nov 201900:11:40

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 Mathers08 Nov 201901:00:45

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.

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Send your stories about our guests and/or your comments to jwolf@asmusa.org.

 

Good Science, Bad Science and How to Make it Better with Ferric Fang and Arturo Casadevall26 Jan 202400:59:07

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

119: Microbiome Diversity and Structural Variation with Ami Bhatt24 Oct 201900:55:19

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:

  • Microbiotarepresents all the organisms that live within a community: archaea, bacteria, viruses, and fungi.
  • Microbiomeis 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.

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118: Lyme Disease and Other Tick-Borne Infections with Jorge Benach11 Oct 201901:03:59

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 Borreliadoesn'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.

Ixodesticks are the vector for Lyme disease and there are 3 stages in the Ixodestick 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 Ambliomaticks (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

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 Bloom26 Sep 201900:52:24

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.

 

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116: Citrus Greening and the Microbiome in Diabetes with Graciela Lorca13 Sep 201900:40:21

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 johnsoniimodulates 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. asiaticuscan't be cultured, Graciela performed a screen on L. asiaticustranscription 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 vivoinfected 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 johnsoniican rescue animals that are predisposed to diabetes. L. johnsoniiinactivates 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. johnsoniias probiotics offers the opportunity to control development of diabetes in predisposed people.

 

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115: 20 Years of the Lab Response Network with Julie Villanueva30 Aug 201900:41:54

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

HOM: The Origin of In Situ Hybridization- a Personal History

114: Global Public Health with George F. Gao15 Aug 201900:45:38

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

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113: Bacteriophage Interactions in the Gut with Jeremy Barr03 Aug 201900:45:38

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:

  1. Follow what excites you! Find an aspect of biology that you're really passionate about and follow that. 
  2. Find amazing mentors. Contact even people you don't directly work with, reach out to them and build your network.
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112: A Career in Salmonella with Stanley Maloy19 Jul 201900:41:24

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.

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111: The Cheese Microbiome with Rachel Dutton03 Jul 201900:38:10

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."

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