John Mekalanos, Ph.D.
Adele Lehman Professor of Microbiology & Molecular Genetics
Department of Microbiology
Harvard Medical School

Protein covariance networks reveal interactions important to the emergence of SARS coronaviruses as human pathogens

SARS-CoV-2 is one of three recognized coronaviruses (CoVs) that have caused epidemics or pandemics in the 21st century and that likely emerged from animal reservoirs based on genomic similarities to bat and civet viruses. Here we report the analysis of conserved interactions between amino acid residues in all proteins encoded by SARS-CoV-related viruses. We identified pairs and networks of residue variants that exhibited statistically high frequencies of covariance with each other. While these interactions are likely key to both protein structure and other protein-protein interactions, we have also found that they can be used for understanding viral evolution and adaptation. Our data provide evidence that the evolutionary processes that converted a bat virus into human pathogen occurred through recombination with other viruses in combination with new adaptive mutations important for entry into human cells.

Lecture: 5 – 6pm

Also available on our branch YouTube channel

Friday December 4th, 2020

Virtual and Live Streamed on YouTube – click here

Morning Session
8:35 A.M. Introduction and Welcome- EPA-ASM student chapter
8:40 A.M. ASM Membership Benefits – Dieter Schifferli, DVM, PhD, President EPA-ASM Chapter
8:45 A.M. Paula Watnick, MD, PhD,
Associate Professor of Pediatrics, Harvard Medical School
“How microbial metabolites control innate immunity and metabolism in a model host intestine”

Graduate Student and Postdoctroal Fellow Presentations
9:45 A.M. Jean-Bernard Lubin, PhD, Postdoctoral Fellow, Children’s Hospital of Philadelphia “A gnotobiotic mouse model of pediatric host-commensal interactions”
10:05 A.M. Break
10:15 A.M. Rina Matsuda, Graduate Student, University of Pennsylvania “Inflammatory monocytes enhance control of Yersinia pseudotuberculosis by intestinal pyogranulomas”
10:35 A.M. Elisha Segrist, Graduate Student, University of Pennsylvania “Microbiota-derived cyclic dinucleotides drive dSTING-dependent enteric antiviral immunity in enterocytes”
10:55 A.M. Ruchika Dehinwal, PhD, Postdoctoral Fellow University of Pennsylvania “Salmonella outer membrane vesicles serve as traps for antibacterial host molecules “

11:15 A.M Poster Sessions and Lunch Break
11:15 A.M. to 12:15 P.M. Odd number poster presentations
12:15 P.M. to 1:15 P.M. Even number poster presentations

Afternoon Session
1:30 P.M. Tajie Harris, PhD
Associate Professor of Neuroscience, University of Virginia School of Medicine
“Alarmin’ the Immune System in the Brain”

Graduate Student and Postdoctoral Fellow Talks
2:30 P.M. Ronald Lucarelli, Graduate Student, Lewis Katz School of Medicine at Temple University “Eicosanoid-activated PPARα inhibits NFκB-dependent Bacterial Clearance during post-Influenza Superinfection”
2:50 P.M. Hager Mohamed, Graduate Student, Drexel University College of Medicine “Exposure to non-thermal plasma increases markers of immunogenicity in a model of latent HIV-1 infection”
3:10 P.M. Break
3:20 P.M. Carolina Rezende Melo-Silva, PhD,  Postdoctoral Fellow, Thomas Jefferson University “Type I interferon receptor signaling coordinates innate immune cells to control an acute viral disease”

3:40 P.M. 2020 Pestka Lecturer
Stanley Plotkin, MD, Emeritus Professor, University of Pennsylvania, Perelman School of Medicine
“The Past, Present, and Future of Vaccines”

4:40 P.M. Presenter Recognition and Poster Presentation Awards* *sponsored by the American Society for Microbiology and PBL Assay Science
5:00 P.M. Meeting Close

Abstract submissions:
see abstract submission guidelines

Please submit all abstracts to

Important Dates:
Oral Presentation Abstract Deadline: November 20th, 2020
Poster Presentation Abstract Deadline: November 25th, 2020
On time Meeting Registration Deadline: December 2nd, 2020

Click to register: PIIF2020registration

Organized by the Eastern Pennsylvania Branch & Student Chapter of the American Society for Microbiology

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

780th Monthly Meeting
September 21, 2020
100th Year Celebration of the Eastern PA Branch ASM
Speakers: James Poupard, Alan Evangelista, Irving Nachamkin, Sunny Shin, Michele Kutzler

781st Monthly Meeting
October 26, 2020
Joe Zackular, University of Pennsylvania
“Microbial cooperation enhances Clostridioides difficile pathogenesis”

782nd Monthly Meeting
November 23rd, 2020
Daniel Portnoy, UC Berkeley
“How intracellular pathogens sense their intracellular environment to activate virulence gene expression”

December 4th 2020
Infection and Immunity Forum

783rd Monthly Meeting
January 25th, 2021
John Mekalanos, Harvard Medical School
“Protein covariance networks reveal interactions important to the emergence of SARS coronaviruses as human pathogens“

784th Monthly Meeting
February 22nd, 2021
Isabell Coppens, Johns Hopkins
“Catching What You Eat: The Secret of the Intracellular Tenure of Toxoplasma gondii

785th Monthly Meeting
March 22nd , 2021
Invited speaker

786th Monthly Meeting
April 26th, 2021
Invited speaker

787th Monthly Meeting
May 24th, 2021
Student Chapter Sponsored Meeting
Student speakers at 4-5pm, Invited Speaker 5-6pm

788th Monthly Meeting
June 14th, 2021
Norman Willett Memorial Lecture
Amy Vollmer, Swarthmore College
“Microbiology: Nevertheless, We Persisted”
(Sponsored by the Education Committee)