Role of the Helicobacter pylori Sensor Kinase ArsS in Protein Trafficking and Acid Acclimation

Helicobacter pylori survives and grows at low pHs via acid acclimation mechanisms that enable periplasmic pH homeostasis. Important components include a cytoplasmic urease; a pH-gated urea channel, UreI; and periplasmic alpha-carbonic anhydrase. To allow the rapid adjustment of periplasmic pH, acid acclimation components are recruited to the inner membrane in acid. The ArsRS two-component system, in an acid-responsive manner, controls the transcription of the urease gene cluster and alpha-carbonic anhydrase. The aim of this study is to determine the role of ArsS in protein trafficking as a component of acid acclimation. H. pylori wild-type and Delta arsS bacteria were incubated at acidic and neutral pHs. Intact bacteria, purified membranes, and total protein were analyzed by Western blotting and urease activity measurements. The total urease activity level was decreased in the Delta arsS strain, but the acid activation of UreI was unaffected. A 30-mb acid exposure increased the level and activity of urease proteins at the membrane in the wild type but not in the Delta arsS strain. The urease levels and activity of the Delta arsS strain after a 90-min acid exposure were similar to those of the wild type. ArsS, in addition to its role in urease gene transcription, is also involved in the recruitment of urease proteins to the inner membrane to augment acid acclimation during acute acid exposure. Urease membrane recruitment following prolonged acid exposure in the absence of ArsS was similar to that of the wild type, suggesting a compensatory mechanism, possibly regulated by FlgS, underscoring the importance of urease membrane recruitment and activation in periplasmic pH homeostasis.