Genetic Evolution of a Helicobacter pylori Acid-Sensing Histidine Kinase and Gastric Disease

J Infect Dis. 2016 Aug 15;214(4):644-8. doi: 10.1093/infdis/jiw189. Epub 2016 May 10.

Abstract

Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, which develops within a hypochlorhydric environment. We sequentially isolated H. pylori (strain J99) from a patient who developed corpus-predominant gastritis and hypochlorhydia over a 6-year interval. Archival J99 survived significantly better under acidic conditions than recent J99 strains. H. pylori arsRS encodes a 2-component system critical for stress responses; recent J99 isolates harbored 2 nonsynonymous arsS mutations, and arsS inactivation abolished acid survival. In vivo, acid-resistant archival, but not recent J99, successfully colonized high-acid-secreting rodents. Thus, genetic evolution of arsS may influence progression to hypochlorhydia and gastric cancer.

Keywords: H. pylori; acid resistance; hypochlorhydia.

MeSH terms

  • Achlorhydria / microbiology*
  • Acids / toxicity
  • Animals
  • Bacterial Proteins / genetics
  • Evolution, Molecular*
  • Gastritis / complications
  • Gastritis / microbiology*
  • Gerbillinae
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / enzymology*
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / isolation & purification
  • Helicobacter pylori / physiology
  • Histidine Kinase / genetics*
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Microbial Viability / drug effects
  • Mutation, Missense

Substances

  • Acids
  • Bacterial Proteins
  • Histidine Kinase