title: NikR mediates nickel-responsive transcriptional repression of the Helicobacter pylori outer membrane proteins FecA3 (HP1400) and FrpB4 (HP1512).
abstract: The transition metal nickel plays an important role in gastric colonization and persistence of the important human pathogen Helicobacter pylori, as it is the cofactor of the abundantly produced acid resistance factor urease. Nickel uptake through the inner membrane is mediated by the NixA protein, and the expression of NixA is controlled by the NikR regulatory protein. Here we report that NikR also controls the nickel-responsive expression of the FecA3 (HP1400) and FrpB4 (HP1512) outer membrane proteins (OMPs), as well as the nickel-responsive expression of an ExbB-ExbD-TonB system, which may function in energization of outer membrane transport. Transcription and expression of the frpB4 and fecA3 genes were repressed by nickel in wild-type H. pylori 26695, but they were independent of nickel and derepressed in an isogenic nikR mutant. Both the frpB4 and fecA3 genes were transcribed from a promoter directly upstream of their start codon. Regulation by NikR was mediated via nickel-dependent binding to specific operators overlapping either the +1 or -10 sequence in the frpB4 and fecA3 promoters, respectively, and these operators contained sequences resembling the proposed H. pylori NikR recognition sequence (TATWATT-N(11)-AATWATA). Transcription of the HP1339-1340-1341 operon encoding the ExbB2-ExbD2-TonB2 complex was also regulated by nickel and NikR, but not by Fur and iron. In conclusion, H. pylori NikR controls nickel-responsive expression of the HP1400 (FecA3) and HP1512 (FrpB4) OMPs. We hypothesize that these two NikR-regulated OMPs may participate in the uptake of complexed nickel ions and that this process is energized by the NikR-regulated ExbB2-ExbD2-TonB2 system, another example of the specific adaptation of H. pylori to the gastric lifestyle.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Room L-455, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Florian D
authors.initials: FD
authors.lastname: Ernst
authors.forename: Jeroen
authors.initials: J
authors.lastname: Stoof
authors.forename: Wannie M
authors.initials: WM
authors.lastname: Horrevoets
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: Arnoud H M
authors.initials: AH
authors.lastname: van Vliet
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics*; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D009532:Nickel / Q000378:metabolism* / Q000494:pharmacology; D009876:Operon / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D009532:Nickel; D007501:Iron