Functional characterization of the pH-sensing ArsRS two-component system of Helicobacter pylori and of its regulon
Final Report Abstract
The ArsRS two-component system is the master regulator of the acid response of H. pylori. By global transcriptome analysis we have defined the complete acid-responsive regulon controlled by the ArsRS two-component system. Bioinformatic analysis of the experimentally defined binding sites of ArsR~P in the promoter regions of selected genes revealed a 23 bp consensus binding motif. Furthermore, we have identified candidate genes which are likely to require the unphosphorylated response regulator ArsR for their transcription control, at least two of which seem to be essential. Lack of expression of these genes might account for the arsR deletion being lethal. Low pH causes the autophosphorylation of the ArsS histidine kinase. We hypothesized that signal perception by the ArsS protein requires protonation of amino acids in the periplasmic input domain. According to the pKa of its side chain, histidine will change its protonation state when the pH drops below 6.0. In fact, we could show that the histidine residue at position 94 is crucial for the efficient induction of the acid response via the histidine kinase ArsS. Moreover, our data suggest that protonation of glutamic and aspartic acid residues is also required to provoke a conformational change of the input domain which triggers the autophosphorylation of ArsS. The contribution of the acidic amino acids to the mechanism of pH sensing is currently investigated in more detail. By the construction of//. pylori mutants expressing the ArsS orthologs HH1607, CJ1262 and WS1818 of//, hepaticus, C. jejuni and W. succinogenes, respectively, we could demonstrate that WSI818 is able to mediate the pH-responsive transcriptional induction of ArsRS target genes via the phosphorylation of ArsR. In contrast, HH1607 and CJ1262 do not respond significantly to low pH.
Publications
- Pflock, M., Finsterer, N., Joseph, B., Mollenkopf, H., Meyer, T.F., and D. Beier. 2006. Characterization of the ArsRS Regulon of Helicobacter pylori, involved in acid adaptation.,/. Bacteriol. 188,3449-3462.
