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Bad Deeds Go Unpunished: The Vacuole Guard Hypothesis and Pathogen Intracellular Growth

Wednesday, November 20, 2019 - 3:00pm to 4:00pm

Speaker

Ralph R. Isberg, Ph.D.
Professor, Molecular Biology and Microbiology
Tufts University School of Medicine

Dr. Isberg has been a professor of molecular biology and microbiology at Tufts University School of Medicine for 32 years. After receiving an undergraduate degree at Oberlin College, he obtained his Ph.D. at Harvard University working on transposable genetic elements in bacteria. Throughout his career at Tufts he has primarily focused on the pathogenesis of Legionella pneumophila and enteropathogenic Yersiniam species, and has recently initiated projects on tackling drug resistance in nosocomial organisms. His research highlights include the identification of proteins involved in the uptake of bacteria into mammalian cells, the identification of the protein machine that allows L. pneumophila to construct an intracellular niche, and understanding how innate immune recognition distinguishes pathogens from nonpathogens. In 2009, he was elected as a member of the National Academy of Sciences. Former trainees from his laboratory include some of the leading figures in the field of bacterial pathogenesis.

Summary

Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably stable, facilitating microbial replication and preventing exposure to host cytoplasmically-localized innate immune sensing mechanisms. To maintain the integrity of the membrane compartment, the pathogen is armed with defensive weapons that prevent loss of vacuole integrity and potential exposure to host innate signaling. In this presentation, Dr. Isberg will present his research that focuses on the growth of the bacterial pathogen Legionella pneumophila within macrophages. This work has allowed the identification of important vacuole guards that are critical for the maintenance of an intact host-derived membrane around the bacterium. He proposes that in the absence of bacterial-encoded guard proteins, aberrant trafficking of host membrane-associated components results in a dysfunctional pathogen compartment that causes loss of vacuole integrity. As a consequence, the host-derived membrane surrounding the bacterium is poisoned and replication is terminated.


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