title: Genetic Evolution of a Helicobacter pylori Acid-Sensing Histidine Kinase and Gastric Disease.
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.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition.
authors.forename: Uma
authors.initials: U
authors.lastname: Krishna
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition.
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.affiliation: Meharry Medical College School of Medicine, Nashville, Tennessee.
authors.forename: Ayeetin
authors.initials: A
authors.lastname: Azah
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University in St Louis, Missouri.
authors.forename: Andrzej M
authors.initials: AM
authors.lastname: Krezel
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Varga
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, Virginia.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Forsyth
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition Department of Cancer Biology, Vanderbilt University School of Medicine.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
mesh_terms: D000126:Achlorhydria / Q000382:microbiology*; D000143:Acids / Q000633:toxicity; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005756:Gastritis / Q000150:complications / Q000382:microbiology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D000071677:Histidine Kinase / Q000235:genetics*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D020125:Mutation, Missense
chemical_list: D000143:Acids; D001426:Bacterial Proteins; D000071677:Histidine Kinase
keywords: H. pylori; acid resistance; hypochlorhydia