ClpP deletion causes attenuation of Salmonella Typhimurium virulence through mis-regulation of RpoS and indirect control of CsrA and the SPI genes
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Bacterial Proteins genetics metabolism MeSH
- Cell Line MeSH
- Gene Deletion * MeSH
- Endopeptidase Clp genetics metabolism MeSH
- Epithelial Cells microbiology MeSH
- Humans MeSH
- Macrophages microbiology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- RNA-Binding Proteins genetics metabolism MeSH
- Gene Expression Regulation, Bacterial * MeSH
- Repressor Proteins genetics metabolism MeSH
- Salmonella typhimurium genetics pathogenicity MeSH
- Sigma Factor genetics metabolism MeSH
- Virulence MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bacterial Proteins MeSH
- Endopeptidase Clp MeSH
- RNA-Binding Proteins MeSH
- Repressor Proteins MeSH
- sigma factor KatF protein, Bacteria MeSH Browser
- Sigma Factor MeSH
- Spi1 protein, Salmonella MeSH Browser
Salmonella enterica serovar Typhimurium requires the type III secretion system encoded by Salmonella pathogenicity island 1 (SPI1) and controlled by the master regulator, HilA, to penetrate the intestinal epithelium. Numerous regulators affect virulence through influence on this system, including the proteolytic component ClpP, the stationary phase regulator RpoS and the carbon-storage regulator CsrA. However, the mechanism behind the ClpP regulation is not fully understood. To elucidate this we examined differentially expressed genes in a ΔclpP mutant compared with WT using global transcriptomic analysis. SPI1 and SPI4 virulence genes were significantly downregulated in the ΔclpP mutant, whereas several RpoS-dependent genes and the fliC gene encoding flagellin were upregulated. While the ΔclpP mutant was attenuated in cell invasion, this attenuation was not present in a ΔclpP/rpoS : : amp double mutant, suggesting the repression of invasion was directed through RpoS. The expression of the csrA virulence regulator was increased in the ΔclpP mutant and decreased in the rpoS : : amp and ΔclpP/rpoS : : amp mutants, indicating that ClpP affects the csrA expression level as well. Thus, this study suggests that ClpP affects SPI1 expression and thereby virulence indirectly through its regulation of both RpoS and CsrA.
Department of Systems Biology Soeltoft Plads Building 221 2800 Kongens Lyngby Denmark
School of Veterinary Medicine and Science University of Nottingham Loughborough LE12 5RD UK
The National Food Institute Technical University of Denmark Moerkhoej Bygade 19 2860 Soeborg Denmark
Veterinary Research Institute Hudcova 70 621 00 Brno Czech Republic
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