Department of Molecular and Cell Biology and Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720

How intracellular pathogens sense their intracellular environment to activate virulence gene expression

Intracellular pathogens collectively cause an enormous amount of world-wide morbidity and mortality.  In my lab, we study Listeria monocytogenes as a very amenable intracellular pathogen as a model for both bacterial pathogenesis and host response.  L. monocytogenes is a Gram-positive, food-borne bacterium that lives a biphasic lifestyle, cycling between a saprophytic existence in the environment and as an intracellular pathogen of mammals. In today’s lecture, I will ask how L. monocytogenes recognizes and responds to the intracellular environment.  I will begin by describing a novel genetic strategy to identify bacterial mutants that fail to up-regulate a virulence factor (ActA) that is not expressed in the environmental phase of growth but becomes the most highly expressed bacterial protein during intracellular growth.  Most of the mutants identified in this screen were in genes that control redox regulation including a gene that encodes glutathione synthase (gshF).  It turns out that both bacterially and to a lesser degree, host-derived glutathione, is the co-factor that activates the central transcriptional virulence activator, PrfA.  In culture, we could recapitulate this response by the addition of glutathione and surprisingly, by adding one of many different reducing agents to the growth media.  The addition of reducing agents caused the up-regulation of gshF, but we still did not know what the precise biological cue was to activate gshF expression.  GshF mutants were 200-fold less virulent in mice while a mutation in PrfA that is locked in its fully active configuration (referred to as PrfA*) completely rescued virulence of a gshF mutant. This led us to look for additional mutants that formed small plaques in tissue culture, but were rescued by the introduction of a PrfA* mutation.  Among the genes identified in this screen was gloA, which encodes glyoxalase A, a component of a glutathione-dependent methylglyoxal (MG) detoxification system. MG is a toxic byproduct of metabolism, which if accumulated, causes DNA damage and protein glycation. As a facultative intracellular pathogen, L. monocytogenes must protect itself from MG produced by its own metabolic processes and that of its host. The gloA mutants grew normally in broth but were sensitive to MG and severely attenuated upon IV infection in mice, but were fully rescued in a PrfA* background. We demonstrate that transcriptional activation of gshF increased upon MG challenge in vitro, yet gloA mutants had decreased levels of GSH, presumably because GSH reacted irreversibly with MG. These data suggest that MG is a host cue that leads to GshF production and activation of PrfA. 

Location: Zoom Virtual Meeting, details to be emailed to Branch Members

For non-members, watch the meeting on our YouTube Channel

Joseph Zackular, Ph.D.
Assistant Professor, Department of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine
Children’s Hospital of Philadelphia

Microbial cooperation enhances Clostridioides difficile pathogenesis

Clostridioides difficile is the most commonly reported nosocomial pathogen in the United States and an urgent public health threat worldwide. The primary risk factor for C. difficile infection of the gastrointestinal tract is antibiotic use, which reduces colonization resistance to C. difficile by perturbing the resident gut microbiota. Despite the well-established link between the gut microbiota and susceptibility to C. difficile infection, the impact of polymicrobial interactions on C. difficile pathogenesis is not well understood.  In this talk, we will explore the effect of microbial cooperation on C. difficile virulence and investigate the molecular mechanisms of cross talk between C. difficile and the gut microbiota.

Please join us for an afternoon of historical and scientific lectures (virtual) to celebrate 100 years of the Eastern Pennsylvania Branch of the American Society for Microbiology. The Eastern PA Branch can trace its origin to February 24, 1920. On this date, Dr David H Bergey invited a group of individuals interested in bacteriology and pathology to attend a meeting in his office on the second floor of the Laboratory of Hygiene, at the University of Pennsylvania (34th Street between Spruce and Walnut). The purpose of the meeting was to organize the Eastern Pennsylvania Chapter of the Society of American Bacteriologists.

Link to Live Meeting on YouTube

Program

4:00 – 4:15 pm Opening Remarks
Dieter M. Schifferli, DVM, Dr Med Vet, Ph.D., University of Pennsylvania, EPAASM Branch President
Victor DiRita, Ph.D., Michigan State University, ASM President

4:15 – 4:45 pm Plenary: Highlights from our First 100 Years
James A. Poupard, Ph.D., Pharma Inst of Philadelphia
After a brief background of Bacteriology in Philadelphia prior to 1920, the 100-year history of our Eastern PA Branch will be presented in five identifiable periods starting in 1920 and culminating in 2020

4:45 – 5:10 pm The Historic and Current Threats of Increasing Antimicrobial Resistance
Alan T. Evangelista, Ph.D., D(ABMM), St. Christopher’s Hospital for Children
A brief review of the major mechanisms of antimicrobial resistance and a focus on key historic milestones in the development of resistance.  Recent changing epidemiologic patterns of multidrug resistance and current/future treatment options will be discussed

5:10 – 5:30 pm A Century of Diagnostic Microbiology Advances with Contributions by the Eastern PA Branch ASM
Irving Nachamkin, Dr.P.H., M.P.H., D(ABMM), FAAM, University of Pennsylvania
This talk will discuss various advances in clinical microbiology diagnostics over the past 100 years, highlighting the contributions of our Branch members

Dr. Nachamkin Bio: Irving Nachamkin is Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania.  He served as the 10th Director of the William Pepper Laboratory of Clinical Medicine, established in 1895 and the first clinical laboratory associated with an academic center, from 2009 to 2020.  He was also the Associate Director of the Clinical Microbiology Laboratory at the Hospital of the University of Pennsylvania from 1982-2020.  Dr Nachamkin has authored or co-authored over 225 peer-reviewed research publications,  reviews and edited several subspecialty books. He has been active with our local branch since the early 80’s and served as Branch President from 1999-2001.  Dr Nachamkin has also been actively involved with our national organization, serving on numerous committees, and was Editor-in-Chief of Clinical Microbiology Reviews from 2002-2012.  He has been recognized for his contributions by election to fellowship in the American Academy of Microbiology,  and is also a fellow of the Infectious Disease Society of America and fellow of the College of Physicians of Philadelphia. Dr. Nachamkin is currently on sabbatical leave and will retire from Penn as Emeritus Professor in January.  

5:30 – 5:50 pm Eavesdropping on Bacterial:Host Conversations: Lessions Learned from Legionnaires’ Disease
Sunny Shin, Ph.D, University of Pennsylvania
In the summer of 1976, an outbreak of a severe pneumonia termed Legionnaires’ Disease occurred among attendees of a Philadelphia convention of the American Legion. This outbreak led to the discovery of the bacterium Legionella pneumophila. Since then, Legionella are now widely recognized as an important cause of community-acquired pneumonia. Legionella has also become a model pathogen studied by many research labs around the world, including several of our branch members. This talk will provide a brief overview of Legionella and highlight the fundamental insights into host cell biology and immunology that have been learned from the study of Legionella

Dr. Shin Bio: Sunny Shin is an Associate Professor in the Department of Microbiology at the University of Pennsylvania Perelman School of Medicine. She received her BS in Biology from MIT, her PhD in Microbiology and Immunology from Stanford University School of Medicine, and her postdoctoral training in the Department of Microbial Pathogenesis at Yale University School of Medicine. Her research program encompasses the fields of bacterial pathogenesis and innate immunity, with a focus on the bacterial pathogens Legionella pneumophila, Coxiella burnetii, and Salmonella Typhimurium. Her laboratory is supported in part by the National Institutes of Health and a Burroughs-Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases Award.

5:50 – 6:10 pm Philadelphia’s Rich History in Vaccine Research and Development: from Empirical Approaches to Advanced Technologies
Michele A. Kutzler, Ph.D., Drexel University School of Medicine
Philadelphia’s rich history of vaccine development stretches back to the 1960s, and many of its highlights came under the direction of collaborating scientists and physicians at institutions and pharma across the city and its suburbs.  This short overview will highlight many of the advances moving from historical empirical approaches to more advanced technologies using recombinant strategies.  Philadelphia left a formidable imprint on vaccine development in the 20th century leading the world forward into the 21st century

6:10 – 7:00 pm Question and Answers and Closing Remarks
Moderators
Toby Eisenstein, Ph.D., Temple University
Linda Miller, Ph.D., CMID Pharma Consulting, LLC

Sandra Urdaneta Hartmann, MD, PhD, MBA
Professor, Department of Microbiology and Immunology
Director, Center for Business and Program Development at the
Institute for Molecular Medicine and Infectious Disease
Drexel University College of Medicine, Philadelphia, PA

E-learning Approaches to Microbiology and Infectious Diseases Education

The COVID-19 pandemic has moved essentially all levels of education to some type of online platform. Regardless of one’s prior experience or training in online instruction, it wasn’t a choice. Many faculty at all levels of the educational spectrum had to learn how to teach online almost overnight; not an easy task. Looking into the future, more widespread online teaching of microbiology in higher education may become part of our “new normal”. The goal of this presentation is to share some tested tips and experiences gained through teaching science online to graduate students. These tips may also be applicable at the undergraduate level. This will be an interactive, live presentation via Zoom. Join us to learn about: (a) effective strategies to offer a supportive, student-centered learning environment online; (b) a few useful resources for teaching microbiology online; and (c) digital game-based learning as an emerging approach for teaching infectious disease concepts.

Time: 5 – 6pm
Place: This was a virtual meeting hosted via Zoom. Watch the lecture below and download a list of online learning resources