Contributions of a LysR transcriptional regulator to Listeria monocytogenes virulence and identification of its regulons.

The capacity of Listeria monocytogenes to adapt to environmental changes is facilitated by a large number of regulatory proteins encoded within its genome. Among these proteins are the uncharacterized LysR-type transcriptional regulators (LTTRs). LTTRs can work as positive and/or negative transcription regulators at both local and global genetic levels. Previously, our group determined by comparative genome analysis that one member of the LTTRs (WP_003734782) was present in pathogenic strains but absent in nonpathogenic strains. The goal of the present study was to assess the importance of this transcription factor in the virulence of L. monocytogenes strain (F2365) and to identify its regulons. L monocytogenes strain lacking lysR (F2365DeltalysR) displayed significant reductions in cell invasion of and adhesion to Caco2 cells. In plaque assays, deletion of lysR resulted in a 42.86% decrease in plaque number and a 13.48% decrease in average plaque size. Furthermore, deletion of lysR also attenuated the virulence of L. monocytogenes in mice following oral and intraperitoneal inoculation. Analysis of transcriptomics revealed that the transcript levels of 139 genes were upregulated while 113 genes were downregulated in the F2365DeltalysR in comparison to wild-type bacteria. lysR-repressed genes included ABC transporters, gene products important for starch and sucrose metabolism as well as glycerolipid metabolism, flagellar assembly, quorum sensing, and glycolysis/gluconeogenesis. Conversely, lysR activated the expression of genes related to fructose and mannose metabolism, cationic antimicrobial peptide (CAMP) resistance, and beta-Lactam resistance. These data suggested that lysR contributed to L. monocytogenes virulence by broad impact on multiple pathways of gene expression.IMPORTANCE: Listeria monocytogenes is the causative agent of listeriosis, an infectious and fatal disease of animals and humans. In this study, we have shown that lysR contributes to Listeria pathogenesis and replication in cell lines. We also highlight the importance of lysR in regulating the transcription of genes involved in different pathways that might be essential for growth and persistence of L. monocytogenes in the host or under nutrient limitation. Better understanding L. monocytogenes pathogenesis and the role of various virulence factors is necessary for further development of prevention and control strategies.