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

In Salmonella typhimurium, the transcription of several virulence genes inc luding spvB is regulated by the PhoP/PhoQ regulatory system. To further exa mine the relationship between the PhoP/PhoQ and Spy systems for virulence i n mice, we examined a non-polar phoP mutation combined with different virul ence plasmid genotypes for effects on virulence of S, typhimurium in the mo use model, PhoP(-)/Spv(+) and PhoP(-)/Spv(-) mutants were not detectably re covered from the spleens of subcutaneously or orally inoculated mice. The p hoP gene constitutively expressed from the lacZ promoter of a low copy numb er 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. Intere stingly, in a PhoP(+) background, the phoP(c) gene reduced splenic infectio n of the Spv(+) but not Spv- salmonellae after subcutaneous or oral inocula tion compared with the PhoP(+) parents. Additionally, the phoP(c) gene in a n Spv(+) background reduced the net growth of salmonellae in macrophages in vitro; phoP(c) in an Spv(-) background was without effect, These data sugg est that the constitutive expression of the phoP gene attenuates the virule nce of S, typhimurium in mice in an Spv-dependent manner.