virK, somA and rcsC Are Important for Systemic Salmonella Enterica Serovar Typhimurium Infection and Cationic Peptide Resistance

Mol Microbiol. 2003 Apr;48(2):385-400. doi: 10.1046/j.1365-2958.2003.03455.x.

Abstract

Salmonella must express and deploy a type III secretion system located in Salmonella pathogenicity island 2 (SPI-2) in order to survive in host phagocytic vacuoles and to cause systemic infection in mouse models of typhoid fever. A genome-wide approach to screening for Salmonella genes that are transcriptionally co-regulated in vitro with SPI-2 genes was used to identify bacterial loci that might function in a mouse model of systemic disease. Strains with mutations in three SPI-2 co-expressed genes were constructed and tested for their ability to cause disease in mice. We found that virK, a homologue of a Shigella virulence determinant, and rcsC, a sensor kinase, are important at late stages of infection. A second Salmonella gene that has VirK homology, somA, is also important for systemic infection in mice. We have shown that expression of both virK and somA requires the transcription factor PhoP, whereas rcsC does not. Additionally, rcsC expression does not require the transcription factor OmpR, but expression of one of the known targets of RcsC, the yojN rcsB putative operon, does require OmpR. virK, somA and rcsC are expressed in tissue culture macrophages and confer Salmonella resistance to the cationic peptide polymyxin B. We conclude that virK, somA and rcsC are important for late stages of Salmonella enteric fever, and that they probably contribute to the remodelling of the bacterial outer membrane in response to the host environment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism*
  • Bacterial Capsules / metabolism
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cells, Cultured
  • Drug Resistance, Bacterial / physiology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Humans
  • Macrophages / cytology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Salmonella Infections / metabolism*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Survival Rate
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Virulence Factors*

Substances

  • Antimicrobial Cationic Peptides
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Multienzyme Complexes
  • SomA protein, Synechococcus lividus
  • Transcription Factors
  • Virulence Factors
  • PhoP protein, Bacteria
  • Protein Kinases
  • Phosphoprotein Phosphatases