Functional characterization of the pH-sensing ArsRS two-component system of Helicobacter pylori and of its regulon

• Applicant: Professorin Dr. Dagmar Beier
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 20067104

The human gastric pathogen Helicobacter pylori is the causative agent of chronic type B gastritis and gastric or duodenal ulcer disease. Moreover, infection with H. pylori is known to be associated with the development of gastric adenocarcinoma and MALT lymphoma. The ability of the neutralophilic bacterium H. pylori to cope with the extremely acidic pH of the stomach lumen is indispensable for the successful colonization of its niche. pH-dependent gene regulation including the control of expression of the essential colonization factor urease is mediated by the ArsRS two-component system via a phosphorelay which is triggered by low pH. However, the observation that arsR is an essential gene, while arsS is not, indicates that additional target genes exist which are not pH-regulated but require the unphosphorylated response regulator ArsR for their transcriptional control. The aim of the present proposal is the characterization of the ArsRS acid response system and the role of unphosphorylated ArsR by the identification of the complete ArsR-dependent regulon. Furthermore, the mechanism of pH-sensing by the periplasmic input domain of the histidine kinase ArsS will be investigated in detail and a functional comparison with the orthologous sensor proteins of related non-gastric members of the ¿-proteobacteria will be performed.

• DFG Programme: Research Grants