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

• Published in: Infection and immunity 2021-03, Vol.89 (4)
• Main Authors: Loh, John T, Shum, Miranda V, Jossart, Scott D R, Campbell, Anne M, Sawhney, Neha, McDonald, W Hayes, Scholz, Matthew B, McClain, Mark S, Forsyth, Mark H, Cover, Timothy L
• Format: Article
• Language: English
• Subjects: Molecular Genomics
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00597-20

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.