Contributions of a LysR Transcriptional Regulator to Listeria monocytogenes Virulence and Identification of Its Regulons
- 1 May 2020
- journal article
- research article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 202 (10)
- https://doi.org/10.1128/JB.00087-20
Abstract
The capacity of Listeria monocytogenes to adapt to environmental changes is facilitated by a large number of regulatory proteins encoded by 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 (NCBI accession no. WP_003734782) was present in pathogenic strains but absent from 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. An L. monocytogenes strain lacking lysR (the F2365 Delta lysR strain) displayed significant reductions in cell invasion of and adhesion to Caco-2 cells. In plaque assays, the deletion of lysR resulted in a 42.86% decrease in plaque number and a 13.48% decrease in average plaque size. Furthermore, the deletion of lysR also attenuated the virulence of L. monocytogenes in mice following oral and intraperitoneal inoculation. The analysis of transcriptomics revealed that the transcript levels of 139 genes were upregulated, while 113 genes were downregulated in the F2365 Delta lysR strain compared to levels in the wild-type bacteria. lysR-repressed genes included ABC transporters, 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 the 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.Funding Information
- HHS | NIH | National Institute of General Medical Sciences (P20 GM103646-07)
This publication has 78 references indexed in Scilit:
- Illuminating the landscape of host–pathogen interactions with the bacterium Listeria monocytogenesProceedings of the National Academy of Sciences of the United States of America, 2011
- Listeria monocytogenes σ B Has a Small Core Regulon and a Conserved Role in Virulence but Makes Differential Contributions to Stress Tolerance across a Diverse Collection of StrainsApplied and Environmental Microbiology, 2010
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- Transcriptome profiling defines a novel regulon modulated by the LysR-type transcriptional regulator MexT in Pseudomonas aeruginosaNucleic Acids Research, 2009
- Transcriptional and post‐transcriptional regulation of the GmaR antirepressor governs temperature‐dependent control of flagellar motility in Listeria monocytogenesMolecular Microbiology, 2009
- Listeria monocytogenes — from saprophyte to intracellular pathogenNature Reviews Microbiology, 2009
- Transcriptome analysis by strand-specific sequencing of complementary DNANucleic Acids Research, 2009
- Regulation of the mpt Operon in Listeria innocua by the ManR ProteinApplied and Environmental Microbiology, 2007
- Listeria monocytogenesFlagella Are Used for Motility, Not as Adhesins, To Increase Host Cell InvasionInfection and Immunity, 2006
- ListeriaPathogenesis and Molecular Virulence DeterminantsClinical Microbiology Reviews, 2001