Meet the Microbiologist

Dr. Maria Gloria Dominguez-Bello, Henry Rutgers Professor of Microbiome and Health and director of the Rutgers-based New Jersey Institute for Food, Nutrition and Health, and Dr. Martin Blaser, Professor of Medicine and Pathology and Laboratory Medicine and director of the Center for Advanced Biotechnology and Medicine at Rutgers (NJ) discuss the importance of preserving microbial diversity in the human microbiome. The pair, whose research was recently featured in a documentary The Invisible Extinction, are on a race to prevent the loss of ancestral microbes and save the bacteria that contribute to human health and well-being.  Links for the Episode: The Invisible Extinction (documentary) Missing Microbes (book) Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (article) (YouTube) Missing Microbes with Dr. Martin Blaser

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.

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.

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.

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.

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

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.

Dr. Linden Hu, Vice Dean for Research at Tufts University in Boston Massachusetts and Paul and Elaine Chervinsky Professor in Immunology, discusses new and ongoing research pertaining to the prevention, treatment and diagnosis of human Lyme disease. He also discusses some of the key unanswered questions about Lyme, such as how B. burgdorferi adapts to different hosts and environments and why some patients have been known to exhibit persistent symptoms even after treatment.   Links mentioned: Webinar - Vector-Borne Disease in a Changing Climate https://asm.org/Webinars/Vector-Borne-Disease-in-a-Changing-Climate The Bulls-Eye Rash of Lyme Disease: https://asm.org/Articles/2018/April/going-skin-deep-investigating-the-cutaneous-host-p Pfizer and Valneva Initiate Phase 3 Study of Lyme Disease Vaccine Candidate VLA15 https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-valneva-initiate-phase-3-study-lyme-disease Could This Treatment Prevent Chronic Lyme Disease? https://news.northeastern.edu/2021/10/06/preventing-chronic-lyme-disease/ Promising New Drug Would Eradicate Lyme While Leaving Gut Microbes Alone: https://www.lymedisease.org/members/lyme-times/2022-spring-news/targeted-lyme-disease-drug/ A Tick’s Meal: https://asm.org/Podcasts/TWiM/Episodes/A-Tick-s-Meal-TWiM-258 Evidence That the Variable Regions of the Central Domain of VlsE Are Antigenic during Infection with Lyme Disease Spirochetes https://journals.asm.org/doi/10.1128/IAI.70.8.4196-4203.2002 Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis of Borrelia burgdorferi and Cytokine Induction https://journals.asm.org/doi/10.1128/IAI.01600-07

Dr. Mark O. Martin, Associate professor of biology at the University of Puget Sound in Tacoma, Washington is a distinguished educator with a well-known social media presence. He discusses how he became interested in microbiology and what drives his varied research foci, including #Microbialcentricity, bacterial predation, bioluminescence, tardigrades, microbial midwives and more. In the process, he delves into his passion for using art and other creative approaches to facilitate learning in the classroom, and shares some experience-driven wisdom about building confidence in STEM. Links for this Episode: Vertically transmitted microbiome protects eggs from fungal infection and egg failure https://animalmicrobiome.biomedcentral.com/articles/10.1186/s42523-021-00104-5 The effects of Sceloporus virgatus cloacal microbiota on the growth of pathogenic fungi https://soundideas.pugetsound.edu/summer_research/426/ Sex-specific asymmetry within the cloacal microbiota of the striped plateau lizard, Sceloporus virgatus https://link.springer.com/article/10.1007/s13199-010-0078-y Predatory Prokaryotes: An Emerging Research Opportunity (pdf) https://www.pugetsound.edu/sites/default/files/file/martin2002_0.pdf Carleton College #LuxArt 2019 https://www.youtube.com/watch?v=fztiJ3o7uWs

Dr. Elizabeth Dinsdale, Matthew Flinders Fellow in Marine Biology in the College of Science and Engineering at Flinders University in Adelaide, Australia, uses genomic techniques to investigate the biodiversity of microbial communities in distinct ecological niches, including coral reefs, kelp forest and shark epidermis. She discusses how shotgun metagenomics is being used to characterize the architecture of microbial communities living in the thin layer of underlying mucus on shark’s skin, and how understanding the function of these microbes is providing clues to important host-microbe interactions, including heavy metal tolerance. Ashley’s Biggest Takeaways: Sharks belong to a subclass of cartilaginous fish called elasmobranchs and are unique in that their epidermises are covered in dermal denticles—overlapping tooth-like structures that reduce drag and turbulence, helping the shark to move quickly and quietly through the water. These dermal denticles are sharp (if you’re going to pet a shark, make sure you go from the head to the tail to avoid getting cut!), and depending on the species of shark, may be more or less spread out across the epidermis. Where do microbes enter the story? Dermal denticles overlay a thin layer of mucus, which provides a distinctive environment for microbial life. Collecting microbial samples from underneath a shark’s dermal denticles is quite difficult, and the technique varies by shark species (shark size, water depth and ability to bite all factor into the equation). Liz’s team uses a specially designed tool that the group affectionately calls a “supersucker,” to create and capture a slurry of microbes and water for analysis. The team then uses shotgun metagenomics to identify and characterize the microbes in their collected samples. Sequencing has revealed biogeographical difference, as well as similarities in microbial architecture of whale sharks across the globe. There are 2 populations of whale sharks—one in the Atlantic Ocean and the other in the Indian Pacific Ocean. Samples collected from both populations have revealed that each individual whale shark, from within each aggregation, shares many of the same microbes. In fact, unlike algae which may share 1 to 2 microbial species, whale sharks share about 80% of microbes across every individual. Since many of the sharks don’t cross aggregations, Liz’s team is investigating the possibility of coevolution between microbes and hosts. Metagenomic sequencing also provides information about the function of the sequenced microbes. High presence of heavy metal-tolerant microbes has been found in the epidermis of all shark species that the team has analyzed. Sharks are known to carry high levels of heavy metals in their skin, muscle and even blood. However, muscle tissue samples contain lower concentrations than skin, indicating that there may be a density gradient in place, and raising questions about how microbes might be involved in this regulation. Is there a pathway by which the microbes metabolize and help to remove concentrations of heavy metals across the epidermis? Liz and her team are hoping to find out. Links: Elizabeth Dinsdale https://www.flinders.edu.au/people/elizabeth.dinsdale Tracking Pathogens via Next Generation Sequencing (NGS) https://asm.org/Magazine/2021/Spring/Tracking-Pathogens-via-Next-Generation-Sequencing Microbial Ecology of Four Coral Atolls in the Northern Line Islands https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001584 Coral Research https://coralandphage.org/research_coral.php  Metagenomic analysis of stressed coral holobionts https://pubmed.ncbi.nlm.nih.gov/19397678/  Metagenomic analysis of the microbial community associated with the coral Porites astreoides  https://pubmed.ncbi.nlm.nih.gov/17922755/