title: Activation of hilA expression at low pH requires the signal sensor CpxA, but not the cognate response regulator CpxR, in Salmonella enterica serovar Typhimurium.
abstract: A two-component regulatory system, cpxR-cpxA, plays an important role in the pH-dependent regulation of virF, a global activator for virulence determinants including invasion genes, in Shigella sonnei. The authors examined whether the cpxR-cpxA homologues have some function in the expression of Salmonella enterica serovar Typhimurium invasion genes via the regulation of hilA, an activator for these genes. In a Salmonella cpxA mutant, the hilA expression level was reduced to less than 10 % of that in the parent strain at pH 6.0. This mutant strain also showed undetectable synthesis of an invasion gene product, SipC, at pH 6.0 and reduced cell invasion capacity - as low as 20 % of that of the parent. In this mutant, the reduction in hilA expression was much less marked at pH 8.0 than at pH 6.0 - no less than 50 % of that in the parent, and no significant reduction was observed in either SipC synthesis or cell invasion rate, compared to the parent. Unexpectedly, a Salmonella cpxR mutant strain and the parent showed no apparent difference in all three characteristics described above at either pH. These results indicate that in Salmonella, the sensor kinase CpxA activates hilA, and consequently, invasion genes and cell invasion capacity at pH 6.0. At pH 8.0, however, CpxA does not seem to have a large role in activation of these factors. Further, the results show that this CpxA-mediated activation does not require its putative cognate response regulator, CpxR. This suggests that CpxA may interact with regulator(s) other than CpxR to achieve activation at low pH.
authors.affiliation: Department of Bacteriology, National Institute of Infectious Diseases, Toyama, 1-23-1, Shinjuku-Ku, Tokyo 162-8640, Japan.
authors.forename: Shu-Ichi
authors.initials: SI
authors.lastname: Nakayama
authors.affiliation: Yakult Central Institute for Microbiological Research, Yaho 1796, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kushiro
authors.affiliation: Yakult Central Institute for Microbiological Research, Yaho 1796, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Asahara
authors.affiliation: Yakult Central Institute for Microbiological Research, Yaho 1796, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Ryu-Ichiro
authors.initials: RI
authors.lastname: Tanaka
authors.affiliation: Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, FDA, Bldg 29, 8800 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Hu
authors.affiliation: Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, FDA, Bldg 29, 8800 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Kopecko
authors.affiliation: Department of Bacteriology, National Institute of Infectious Diseases, Toyama, 1-23-1, Shinjuku-Ku, Tokyo 162-8640, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C102236:HilA protein, Salmonella; C094578:Salmonella invasion protein C; D015534:Trans-Activators; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C092472:CpxA protein, bacteria