title: An ABC transporter and a TonB ortholog contribute to Helicobacter mustelae nickel and cobalt acquisition.
abstract: The genomes of Helicobacter species colonizing the mammalian gastric mucosa (like Helicobacter pylori) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. In this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen Helicobacter mustelae. The expression of the outer membrane protein-encoding frpB2 gene was iron and Fur repressed, whereas the expression of the ABC transporter genes fecD and ceuE was iron and Fur independent. The inactivation of the two tonB genes showed that TonB1 is required for heme utilization, whereas the absence of TonB2 only marginally affected iron-dependent growth but led to reduced cellular nickel content and urease activity. The inactivation of the fecD and ceuE ABC transporter genes did not affect iron levels but resulted in significantly reduced urease activity and cellular nickel content. Surprisingly, the inactivation of the nixA nickel transporter gene affected cellular nickel content and urease activity only when combined with the inactivation of other nickel acquisition genes, like fecD or ceuE. The FecDE ABC transporter is not specific for nickel, since an fecD mutant also showed reduced cellular cobalt levels and increased cobalt resistance. We conclude that the H. mustelae fecDE and ceuE genes encode an ABC transporter involved in nickel and cobalt acquisition, which works independently of the nickel transporter NixA, while TonB2 is required primarily for nickel acquisition, with TonB1 being required for heme utilization.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Stoof
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Gerard
authors.initials: G
authors.lastname: Klaver
authors.forename: Arnoud H M
authors.initials: AH
authors.lastname: van Vliet
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D003035:Cobalt / Q000378:metabolism*; D005289:Ferrets; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D016680:Genome, Bacterial; D045502:Helicobacter mustelae / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009532:Nickel / Q000378:metabolism*; D014510:Urease / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D008565:Membrane Proteins; C057616:tonB protein, Bacteria; D003035:Cobalt; D009532:Nickel; D014510:Urease