title: Iron and pH homeostasis intersect at the level of Fur regulation in the gastric pathogen Helicobacter pylori.
abstract: Helicobacter pylori persistently colonizes the stomach of the majority of the world's population and is a tremendous medical burden due to its causal role in diverse gastric maladies. Since the stomach is a constantly changing environment, successful colonization of H. pylori within this niche requires regulation of bacterial gene expression to cope with the environmental fluctuations. In H. pylori, the ferric uptake regulator (Fur) has been shown to play an intricate role in adaptation of the bacterium to two conditions known to oscillate within the gastric mucosa: iron limitation and low pH. To extend our knowledge of the process of regulation and adaptation in H. pylori, we show that Fur is required for efficient colonization of the Mongolian gerbil: the mutant strain exhibits a 100-fold increase in the 50% infectious dose, as well as a 100-fold defect in competitive colonization, when coinfected with wild-type bacteria. Furthermore, we used DNA microarrays to identify genes whose expression was altered in a Fur-deficient strain. We show that the Fur regulon of H. pylori consists of approximately 30 genes, most of which have been previously annotated as acid stress associated. Finally, we investigate the role of Fur in acid-responsive modulation of gene expression and show that a large number of genes are aberrantly expressed in the Fur mutant specifically upon acid exposure. This fact likely explains the requirement for this regulator for growth and colonization in the stomach.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Hanan
authors.initials: H
authors.lastname: Gancz
authors.forename: Stefano
authors.initials: S
authors.lastname: Censini
authors.forename: D Scott
authors.initials: DS
authors.lastname: Merrell
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000502:physiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron