title: The Helicobacter pylori homologue of the ferric uptake regulator is involved in acid resistance.
abstract: The only known niche of the human pathogen Helicobacter pylori is the gastric mucosa, where large fluctuations of pH occur, indicating that the bacterial response and resistance to acid are important for successful colonization. One of the few regulatory proteins in the H. pylori genome is a homologue of the ferric uptake regulator (Fur). In most bacteria, the main function of Fur is the regulation of iron homeostasis. However, in Salmonella enterica serovar Typhimurium, Fur also plays an important role in acid resistance. In this study, we determined the role of the H. pylori Fur homologue in acid resistance. Isogenic fur mutants were generated in three H. pylori strains (1061, 26695, and NCTC 11638). At pH 7 there was no difference between the growth rates of mutants and the parent strains. Under acidic conditions, growth of the fur mutants was severely impaired. No differences were observed between the survival of the fur mutant and parent strain 1061 after acid shock. Addition of extra iron or removal of iron from the growth medium did not improve the growth of the fur mutant at acidic pH. This indicates that the phenotype of the fur mutant at low pH was not due to increased iron sensitivity. Transcription of fur was repressed in response to low pH. From this we conclude that Fur is involved in the growth at acidic pH of H. pylori; as such, it is the first regulatory protein implicated in the acid resistance of this important human pathogen.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Jetta J E
authors.initials: JJ
authors.lastname: Bijlsma
authors.forename: Barbara
authors.initials: B
authors.lastname: Waidner
authors.forename: Arnoud H M van
authors.initials: AH
authors.lastname: Vliet
authors.forename: Nicky J
authors.initials: NJ
authors.lastname: Hughes
authors.forename: Stephanie
authors.initials: S
authors.lastname: Häg
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Christina M J E
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
authors.forename: Manfred
authors.initials: M
authors.lastname: Kist
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
mesh_terms: D000143:Acids / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D003470:Culture Media; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000494:pharmacology; D016296:Mutagenesis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014510:Urease / Q000378:metabolism
chemical_list: D000143:Acids; D001426:Bacterial Proteins; D003470:Culture Media; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron; D014510:Urease; D006851:Hydrochloric Acid