ARS | Publication request: COMPARISON OF VIRULENCE IN MICE AND CACO-2 CELL INVASION BY MUTANTS OF THE PUTATIVE CRP/FNR FAMILY OF TRANSCRIPTIONAL REGULATORS OF A SEROTYPE 4B STRAIN OF LISTERIA MONOCYTOGENES

Submitted to: Meeting Abstract
Publication Acceptance Date: June 30, 2004
Publication Date: May 17, 2004
Citation: Czuprynski, C., Uhlich, G.A., Wonderling, L.D., Faith, N., Neudeck, B., Loeb, J., Luchansky, J.B. 2004. Comparison Of Virulence In Mice And Caco-2 Cell Invasion By Mutants Of The Putative Crp/fnr Family Of Transcriptional Regulators Of A Serotype 4b Strain Of Listeria Monocytogenes. Meeting Abstract.

Technical Abstract: Listeria monocytogenes is an important food-borne pathogen that causes considerable morbidity and mortality. Our ability to effectively predict the risk posed by L. monocytogenes contamination is limited in part by our incomplete understanding of what virulence mechanisms allow L. monocytogenes to survive in the harsh environment of the g.i. tract, or to translocate across the intestinal mucosa and cause systemic disease. A series of transposon mutants of the Crp/Fnr family of transcriptional regulators in L. monocytogenes were derived from a serotype 4b strain (F2365) originally isolated from cheese (i.e. Jalisco) in a large food-borne outbreak in California. Most previous studies of the molecular pathogenesis of listeriosis have used laboratory strains of L. monocytogenes. These mutants will help us understand how the response of L. monocytogenes to the various environmental conditions it might encounter when introduced into a food product, affect its ability to invade and cause systemic disease following entry into the gastrointestinal tract. We have evaluated these mutant strains for virulence in the A/J mouse model of gastrointestinal listeriosis that we have reported previously. To date, we have identified 3 mutant stains that appear to be of somewhat increased virulence, and one strain that is essentially avirulent in the A/J mouse model of gastrointestinal listeriosis. The latter strain does persist in the g.i. tract, infect the gall bladder and sporadically seed the bloodstream without establishing progressive infection in the spleen and liver. We have also compared these strains for their ability to invade the Caco-2 human intestinal epithelial cell line and find that the avirulent strain has a diminished ability to invade and multiply in differentiated Caco-2 cells. Oral infection with the avirulent mutant conferred some protection to mice that were subsequently challenged e.g. with the virulent parent strain. This approach will help to better define environmental conditions (e.g. nutrients, temperature) and virulence determinants that affect the pathogenesis of gastrointestinal listeriosis.