Histidine Residue 94 Is Involved in pH Sensing by Histidine Kinase ArsS of Helicobacter pylori

Abstract

BackgroundThe ArsRS two-component system is the master regulator of acid adaptation in the human gastric pathogen Helicobacter pylori. Low pH is supposed to trigger the autophosphorylation of the histidine kinase ArsS and the subsequent transfer of the phosphoryl group to its cognate response regulator ArsR which then acts as an activator or repressor of pH-responsive genes. Orthologs of the ArsRS two-component system are also present in H. pylori's close relatives H. hepaticus, Campylobacter jejuni and Wolinella succinogenes which are non-gastric colonizers.Methodology/Principal FindingsIn order to investigate the mechanism of acid perception by ArsS, derivatives of H. pylori 26695 expressing ArsS proteins with substitutions of the histidine residues present in its periplasmic input domain were constructed. Analysis of pH-responsive transcription of selected ArsRS target genes in these mutants revealed that H94 is relevant for pH sensing, however, our data indicate that protonatable amino acids other than histidine contribute substantially to acid perception by ArsS. By the construction and analysis of H. pylori mutants carrying arsS allels from the related ε-proteobacteria we demonstrate that WS1818 of W. succinogenes efficiently responds to acidic pH.Conclusions/SignificanceWe show that H94 in the input domain of ArsS is crucial for acid perception in H. pylori 26695. In addition our data suggest that ArsS is able to adopt different conformations depending on the degree of protonation of acidic amino acids in the input domain. This might result in different activation states of the histidine kinase allowing a gradual transcriptional response to low pH conditions. Although retaining considerable similarity to ArsS the orthologous proteins of H. hepaticus and C. jejuni may have evolved to sensors of a different environmental stimulus in accordance with the non gastric habitat of these bacteria.

Acis-Encoded Antisense Small RNA Regulated by the HP0165-HP0166 Two-Component System Controls Expression ofureBinHelicobacter pylori

“…The histidine kinase sensor senses low pH due to a histidine residue 94 (H94) in the periplasmic input domain (37) and triggers autophosphorylation of HP0165 and the subsequent phosphorylation of its cognate response regulator HP0166. The phosphorylated response regulator then binds to extended regions overlapping the P ureA and P ureI promoters (41) to positively regulate the transcription of urease genes.…”

Repetitive Sequence Variations in the Promoter Region of the Adhesin-Encoding Gene sabA of Helicobacter pylori Affect Transcription

“…This allows adaption to environmental changes at the transcriptional level (17)(18)(19)(20)(21)(22)(23). When the histidine kinase protein of a TCST encounters the appropriate stimulus, it undergoes autophosphorylation; subsequently, the phosphoryl group is transferred to a response regulator.…”

Helicobacter pylori 5'ureB-sRNA, a cis-Encoded Antisense Small RNA, Negatively Regulates ureAB Expression by Transcription Termination

“…In H. pylori, UreA and UreB are the enzymatically active subunits of the urease enzyme necessary for cytoplasmic and periplasmic pH homeostasis and are present as inactive apoenzyme until nickel insertion by UreE, -F, -G, and -H. Transcription of the ureAB operon is positively regulated by the ArsRS two-component system (18,20). The periplasmic histidine kinase sensor ArsS perceives lowering of medium pH via protonation of its histidine residue 94 (H94) in the periplasmic input domain (36) and triggers autophosphorylation and subsequent phosphorylation of its cognate response regulator ArsR. The phosphorylated response regulator ArsR (ArsRϳP) then binds to extended regions overlapping the P ureA promoters (20) to activate the transcription of ureAB into a 2.7-kb mRNA coding for functional UreA and UreB.…”