Delineation of the pH-Responsive Regulon Controlled by the Helicobacter pylori ArsRS Two-Component System.

encounters a wide range of pH within the human stomach. In a comparison of cultured under neutral or acidic conditions, about 15% of genes are differentially expressed, and corresponding changes are detectable for many of the encoded proteins. The ArsRS two-component system (TCS), comprised of the sensor kinase ArsS and its cognate response regulator ArsR, has an important role in mediating pH-responsive changes in gene expression. In this study, we sought to delineate the pH-responsive ArsRS regulon and further define the role of ArsR in pH-responsive gene expression. We compared strains containing an intact ArsRS system with an null mutant or strains containing site-specific mutations of a conserved aspartate residue (D52) in ArsR, which is phosphorylated in response to signals relayed by the cognate sensor kinase ArsS. We identified 178 genes that were pH-responsive in strains containing an intact ArsRS system but not in Δ or mutants. These constituents of the pH-responsive ArsRS regulon include genes involved in acid acclimatization (, amidases), oxidative stress responses (, ), transcriptional regulation related to iron or nickel homeostasis (, ), and genes encoding outer membrane proteins (including , , , [], and ). When comparing strains containing an intact ArsRS TCS with mutants, each cultured at neutral pH, relatively few genes are differentially expressed. Collectively, these data suggest that ArsRS-mediated gene regulation has an important role in adaptation to changing pH conditions.