Polymorphisms of the acid sensing histidine kinase gene arsS in Helicobacter pylori populations from anatomically distinct gastric sites

Abstract

Phase variation is frequently utilized by bacterial species to affect gene expression such that phenotypic variants are maintained within populations, ensuring survival as environmental or host conditions change. Unusual among Helicobacter pylori phase variable or contingency genes is arsS, encoding a sensory histidine kinase involved in the acid acclimation of the organism. The presence of a 3′ homopolymeric cytosine tract of variable length in arsS among Helicobacter pylori strains allows for the expression of various functional ArsS isoforms, differing in carboxy-terminal protein domains. In this study, we analyzed this 3′ arsS region via amplified fragment length polymorphism (AFLP) and sequencing analyses for H. pylori populations from 3 different gastric sites of 12 patients. Our data indicate the presence of multiple arsS alleles within each population of H. pylori derived from the gastric antrum, cardia, or corpus of these patients. We also show that H. pylori, derived from the same anatomical site and patient, are predicted to express multiple ArsS isoforms in each population investigated. Furthermore, we identify a polymorphic deletion within arsS that generates another alternate ArsS C-terminal end. These findings suggest that four C-terminal variations of ArsS adds to the complexity of the ArsRS acid adaptation mechanism as a whole and may influence the ability of H. pylori to persist in the gastric niche for decades.

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

“…AFLP analysis. To quantify the degree of slipped-strand mispairing and the variation in poly(T) length found in the J99 wild type, J99 T18 control mutant, and J99 sabA poly(T) variant populations of H. pylori, AFLP was conducted by a modification of the protocol of Hallinger et al (29). Briefly, an oligonucleotide primer pair bracketing the poly(T) tract was synthesized with a VIC tag on the 5= end of the reverse primer (Applied Biosystems/Life Technologies).…”

Genetic Evolution of aHelicobacter pyloriAcid-Sensing Histidine Kinase and Gastric Disease

“…As acidity increases, ArsS undergoes autophosphorylation at histidine 214 within the cytoplasmic kinase domain. Phosphorylated histidine 214 subsequently transfers the phosphate residue to aspartic acid residue 52 on ArsR [5][6][7], liberating ArsR to function as a transcription factor regulating expression of urease complex components, amidases, and carbonic anhydrase [5][6][7]. These data suggest that modifications in the ability to respond to gastric acid may differ in H. pylori strains predisposed to the development of intestinal-type gastric adenocarcinoma.…”

“…H. pylori has evolved to survive under highly acidic conditions, and one mechanism that underpins the acid-resistant phenotype is production of urease [5][6][7]. Another constituent used by H. pylori within this context is the ArsRS 2-component (ArsR and ArsS) signal transduction system, which regulates genes involved in acid resistance, including urease [5,6].…”

“…pylori has evolved to survive under highly acidic conditions, and one mechanism that underpins the acid-resistant phenotype is production of urease [5][6][7]. Another constituent used by H. pylori within this context is the ArsRS 2-component (ArsR and ArsS) signal transduction system, which regulates genes involved in acid resistance, including urease [5,6]. ArsS is the sensory constituent of this 2-component system, and the periplasmic domain of ArsS is required to detect external changes in pH, whereas ArsR is the response component.…”