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Updated: Jul 29, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Constitutively expressed phoP inhibits mouse-virulence of Salmonella typhimurium in an Spv-dependent manner
H Matsui1, T Kawakami, S Ishikawa
1Laboratory of Infectious Diseases and Immunology, Center for Basic Research, The Kitasato Institute, Tokyo, Japan. matsui-h@kitasato.or.jp
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.
Insights
Constitutive expression of the phoP gene attenuates Salmonella typhimurium virulence in mice. This attenuation is dependent on the Spv system, impacting bacterial growth in macrophages.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- The PhoP/PhoQ system regulates virulence genes, including spvB, in Salmonella typhimurium.
- Understanding the interplay between PhoP/PhoQ and the Spv system is crucial for Salmonella virulence research.
Purpose of the Study:
- To investigate the relationship between the PhoP/PhoQ regulatory system and the Spv system in Salmonella typhimurium virulence in a mouse model.
- To assess the impact of constitutive phoP expression on S. typhimurium virulence and growth.
Main Methods:
- Construction and analysis of non-polar phoP mutants in S. typhimurium with varying virulence plasmid (Spv) genotypes.
- Evaluation of bacterial recovery from mouse spleens after subcutaneous and oral inoculation.
- Assessment of bacterial growth in macrophages in vitro.
- Complementation studies using a constitutively expressed phoP gene (phoP(C)).
Main Results:
- PhoP-deficient mutants (PhoP-/Spv+ and PhoP-/Spv-) were not recovered from mouse spleens, indicating a critical role for PhoP in systemic infection.
- Constitutive expression of phoP (phoP(C)) partially complemented the phoP mutation but resulted in reduced virulence compared to wild-type strains.
- In a PhoP+ background, phoP(C) significantly reduced splenic infection in an Spv-dependent manner.
- phoP(C) in an Spv+ background decreased Salmonella growth in macrophages in vitro, while it had no effect in an Spv- background.
Conclusions:
- Constitutive expression of the phoP gene attenuates Salmonella typhimurium virulence in mice.
- The attenuating effect of constitutive phoP expression is Spv-dependent.
- The PhoP/PhoQ system and the Spv system exhibit a complex interaction influencing Salmonella pathogenesis.
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