Interplay Between c-di-GMP Signaling, Metabolism and Virulence in Listeria Monocytogenes

<p>Gomelsky, M, PISUMMARYListeria monocytogenes is one of the most problematic causative agents of foodborne illness. Despite arelatively low number of cases, listeriosis is ranked as the deadliest and the fourth costliest foodborne diseasein the USA among all diseases caused by bacterial, parasitic and viral foodborne pathogens. We havecharacterized a major regulatory system involving the second messenger, c-di-GMP, in L. monocytogenes andfound that it plays unexpectedly important roles at the interface between the saprophitic and the pathogeniclifestyles of this bacterium. One of the consequences of elevated intracellular c-di-GMP levels is severeinhibition of mammalian cell invasion. This project is aimed at (i) deciphering the mechanism of c-di-GMP-dependent inhibition of cell invasion, which appears to involve key regulators of biosynthesis and virulence,and (ii) identifying natural compounds that strongly affect intracellular c-di-GMP levels in L. monocytogenes.This project is expected to shed light onto the interplay between c-di-GMP signaling, metabolism and virulencein L. monocytogenes that is emerging as a novel regulatory paradigm. Results of this project may also lead toidentifying natural compounds that inhibit listerial invasiveness and therefore may be used to reduce frequencyof listerial infections.</p>