Knudsen, Gitte Maegaard5; Olsen, John E.6; Aabo, Søren3; Barrow, Paul7; Rychlik, Ivan9; Thomsen, Line E.6
1 Department of Systems Biology, Technical University of Denmark2 Center for Systems Microbiology, Department of Systems Biology, Technical University of Denmark3 National Food Institute, Technical University of Denmark4 Division of Food Microbiology, National Food Institute, Technical University of Denmark5 Bacterial Ecophysiology and Biotechnology, Department of Systems Biology, Technical University of Denmark6 University of Copenhagen7 University of Nottingham8 Veterinary Research Institute9 Veterinary Research Institute
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.
Microbiology, 2013, Vol 159, Issue Part 7, p. 1497-1509
The Faculty of Health and Medical Sciences; salmonella; virulens; protease