Constitutively expressed phoP inhibits mouse-virulence of Salmonella typhimurium in an Spv-dependent manner

Microbiol Immunol. 2000;44(6):447-54. doi: 10.1111/j.1348-0421.2000.tb02519.x.

Abstract

In Salmonella typhimurium, the transcription of several virulence genes including spvB is regulated by the PhoP/PhoQ regulatory system. To further examine the relationship between the PhoP/PhoQ and Spv systems for virulence in mice, we examined a non-polar phoP mutation combined with different virulence plasmid genotypes for effects on virulence of S. typhimurium in the mouse model. PhoP-/Spv+ and PhoP-/Spv- mutants were not detectably recovered from the spleens of subcutaneously or orally inoculated mice. The phoP gene constitutively expressed from the lacZ promoter of a low copy number vector (phoP(C)) only partially complemented the non-polar phoP mutation for mouse-virulence in both the Spv+ and Spv- backgrounds; both PhoP(C) strains exhibited virulence equal only to a PhoP+/Spv- strain. Interestingly, in a PhoP+ background, the phoP(C) gene reduced splenic infection of the Spv+ but not Spv- salmonellae after subcutaneous or oral inoculation compared with the PhoP+ parents. Additionally, the phoP(C) gene in an Spv+ background reduced the net growth of salmonellae in macrophages in vitro; phoP(C) in an Spv- background was without effect. These data suggest that the constitutive expression of the phoP gene attenuates the virulence of S. typhimurium in mice in an Spv-dependent manner.

Publication types

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

MeSH terms

  • ADP Ribose Transferases / genetics
  • ADP Ribose Transferases / metabolism*
  • Administration, Oral
  • Animals
  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / genetics
  • Cell Line
  • Female
  • Gene Expression Regulation
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Genotype
  • Injections, Subcutaneous
  • Lac Operon
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mutagenesis
  • Operon
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity*
  • Spleen / cytology
  • Stem Cells / cytology
  • Virulence
  • Virulence Factors*

Substances

  • Bacterial Proteins
  • Recombinant Fusion Proteins
  • Virulence Factors
  • PhoP protein, Bacteria
  • ADP Ribose Transferases
  • spvB protein, Salmonella enterica virulence plasmid