title: Constitutively expressed phoP inhibits mouse-virulence of Salmonella typhimurium in an Spv-dependent manner.
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.
authors.affiliation: Laboratory of Infectious Diseases and Immunology, Center for Basic Research, The Kitasato Institute, Tokyo, Japan. matsui-h@kitasato.or.jp
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: T
authors.initials: T
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.forename: H
authors.initials: H
authors.lastname: Danbara
authors.forename: P A
authors.initials: PA
authors.lastname: Gulig
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005838:Genotype; D007279:Injections, Subcutaneous; D007763:Lac Operon; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009876:Operon; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D014774:Virulence; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; C061064:PhoP protein, Bacteria; D036002:ADP Ribose Transferases; C415223:spvB protein, Salmonella enterica virulence plasmid