title: Helicobacter pylori adaptation in vivo in response to a high-salt diet.
abstract: Helicobacter pylori exhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification of H. pylori is influenced by the composition of the diet. Specifically, we investigated the effect of a high-salt diet (a known risk factor for gastric adenocarcinoma) on H. pylori diversification within a host. We analyzed H. pylori strains isolated from Mongolian gerbils fed either a high-salt diet or a regular diet for 4 months by proteomic and whole-genome sequencing methods. Compared to the input strain and output strains from animals fed a regular diet, the output strains from animals fed a high-salt diet produced higher levels of proteins involved in iron acquisition and oxidative-stress resistance. Several of these changes were attributable to a nonsynonymous mutation in fur (fur-R88H). Further experiments indicated that this mutation conferred increased resistance to high-salt conditions and oxidative stress. We propose a model in which a high-salt diet leads to high levels of gastric inflammation and associated oxidative stress in H. pylori-infected animals and that these conditions, along with the high intraluminal concentrations of sodium chloride, lead to selection of H. pylori strains that are most fit for growth in this environment.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Loh
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gaddy
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
authors.forename: Holly M Scott
authors.initials: HM
authors.lastname: Algood
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA School of Anatomy, Physiology, and Human Biology, University of Western Australia, Nedlands, Western Australia, Australia Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA timothy.l.cover@vanderbilt.edu.
authors.forename: Timothy L
authors.identifier: http://orcid.org/0000-0001-8503-002X
authors.initials: TL
authors.lastname: Cover
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D004195:Disease Models, Animal; D005753:Gastric Mucosa; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D020543:Proteome; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D012097:Repressor Proteins; D017673:Sodium Chloride, Dietary; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron