Title:
The intersection of bacterial metabolism, pathogenesis, and innate immunity
Daniel Portnoy, PhD
Professor of Biochemistry, Biophysics and Structural Biology
and Affiliate, Division of Immunology & Pathogenesis
University of California, Berkeley, Dept. of Molecular and Cell Biology
Faculty Host: Gregory A. Smith, PhD
Topic:
My laboratory studies the pathogenesis of Listeria monocytogenes as a model intracellular pathogen that is highly amenable to experimental analysis in vitro, in tissue culture and in mice. In my seminar at Northwestern, I will discuss three examples that we are working on in which a bacterial metabolite activates host innate immunity. I will focus on the relationship of L. monocytogenes and flavin metabolism. L. monocytogenes requires host flavins for growth and we show that although they can grow on riboflavin extracellularly, they obtain the in cells and in mice by importing FMN and FAD directly from their host cells. A mutant that is unable to synthesize FMN and FAD still grows extracellularly, but is unable to grow extracellularly in vivo. We engineered a strain of L. monocytogenes that can synthesize riboflavin and find that it is 100-fold less virulent because a population of innate T-cells called MAIT cells that are activated by an intermediate of riboflavin biosynthesis. These results are suggest that avoidance of MAIT cells represents an aspect of L. monocytogenes pathogenesis.
Cynthia Naugles
(312) 503-0489
Email