ClpP deletion causes attenuation of Salmonella Typhimurium virulence through mis-regulation of RpoS and indirect control of CsrA and the SPI genes
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ClpP deletion causes attenuation of Salmonella Typhimurium virulence through mis-regulation of RpoS and indirect control of CsrA and the SPI genes. / Knudsen, Gitte Maegaard; Olsen, John Elmerdahl; Aabo, Søren; Barrow, Paul; Rychlik, Ivan; Thomsen, Line E.
In: Microbiology, Vol. 159, No. 7, 2013, p. 1497-1509.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - ClpP deletion causes attenuation of Salmonella Typhimurium virulence through mis-regulation of RpoS and indirect control of CsrA and the SPI genes
AU - Knudsen, Gitte Maegaard
AU - Olsen, John Elmerdahl
AU - Aabo, Søren
AU - Barrow, Paul
AU - Rychlik, Ivan
AU - Thomsen, Line E
PY - 2013
Y1 - 2013
N2 - 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 wild-type using global transcriptomic analysis. SPI1 and SPI4 virulence genes were significantly down-regulated in the ΔclpP mutant whereas several RpoS-dependent genes and the fliC gene encoding flagellin were up-regulated. 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.
AB - 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 wild-type using global transcriptomic analysis. SPI1 and SPI4 virulence genes were significantly down-regulated in the ΔclpP mutant whereas several RpoS-dependent genes and the fliC gene encoding flagellin were up-regulated. 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.
KW - Faculty of Health and Medical Sciences
KW - salmonella
KW - virulens
KW - protease
U2 - 10.1099/mic.0.065797-0
DO - 10.1099/mic.0.065797-0
M3 - Journal article
C2 - 23676436
VL - 159
SP - 1497
EP - 1509
JO - Microbiology
JF - Microbiology
SN - 1350-0872
IS - 7
ER -
ID: 46895298