title: Phosphorylation-dependent and Phosphorylation-independent Regulation of Helicobacter pylori Acid Acclimation by the ArsRS Two-component System.
abstract: BACKGROUND
  The pH-sensitive Helicobacter pylori ArsRS two-component system (TCS) aids survival of this neutralophile in the gastric environment by directly sensing and responding to environmental acidity. ArsS is required for acid-induced trafficking of urease and its accessory proteins to the inner membrane, allowing rapid, urea-dependent cytoplasmic and periplasmic buffering. Expression of ArsR, but not its phosphorylation, is essential for bacterial viability. The aim of this study was to characterize the roles of ArsS and ArsR in the response of H. pylori to acid.
  
  
  METHODS
  Wild-type H. pylori and an arsR(D52N) phosphorylation-deficient strain were incubated at acidic or neutral pH. Gene and protein expression, survival, membrane trafficking of urease proteins, urease activity, and internal pH were studied.
  
  
  RESULTS
  Phosphorylation of ArsR is not required for acid survival. ArsS-driven trafficking of urease proteins to the membrane in acid, required for recovery of internal pH, is independent of ArsR phosphorylation. ArsR phosphorylation increases expression of the urease gene cluster, and the loss of negative feedback in a phosphorylation-deficient mutant leads to an increase in total urease activity.
  
  
  CONCLUSIONS
  ArsRS has a dual function in acid acclimation: regulation of urease trafficking to UreI at the cytoplasmic membrane, driven by ArsS, and regulation of urease gene cluster expression, driven by phosphorylation of ArsR. ArsS and ArsR work through phosphorylation-dependent and phosphorylation-independent regulatory mechanisms to impact acid acclimation and allow gastric colonization. Furthering understanding of the intricacies of acid acclimation will impact the future development of targeted, nonantibiotic treatment regimens.
authors.affiliation: Department of Pediatrics, DGSOM at UCLA, Los Angeles, CA, 90095, USA.|VA GLAHS, Los Angeles, CA, 90073, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Marcus
authors.affiliation: VA GLAHS, Los Angeles, CA, 90073, USA.|Department of Physiology, DGSOM at UCLA, Los Angeles, CA, 90095, USA.|Department of Medicine, DGSOM at UCLA, Los Angeles, CA, 90095, USA.
authors.forename: George
authors.initials: G
authors.lastname: Sachs
authors.affiliation: VA GLAHS, Los Angeles, CA, 90073, USA.|Department of Physiology, DGSOM at UCLA, Los Angeles, CA, 90095, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.affiliation: VA GLAHS, Los Angeles, CA, 90073, USA.|Department of Physiology, DGSOM at UCLA, Los Angeles, CA, 90095, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Scott
mesh_terms: D000143:Acids / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D021381:Protein Transport; D014510:Urease / Q000235:genetics / Q000378:metabolism
chemical_list: D000143:Acids; D001426:Bacterial Proteins; D014510:Urease
keywords: ArsRS; Helicobacter pylori; acid acclimation; two-component system; urease