title: NikR mediates nickel-responsive transcriptional induction of urease expression in Helicobacter pylori.
abstract: The important human pathogen Helicobacter pylori requires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity of H. pylori urease were previously demonstrated to be induced by nickel supplementation of growth media. Here it is demonstrated that the HP1338 protein, an ortholog of the Escherichia coli nickel regulatory protein NikR, mediates nickel-responsive induction of urease expression in H. pylori. Mutation of the HP1338 gene (nikR) of H. pylori strain 26695 resulted in significant growth inhibition of the nikR mutant in the presence of supplementation with NiCl(2) at > or =100 microM, whereas the wild-type strain tolerated more than 10-fold-higher levels of NiCl(2). Mutation of nikR did not affect urease subunit expression or urease enzyme activity in unsupplemented growth media. However, the nickel-induced increase in urease subunit expression and urease enzyme activity observed in wild-type H. pylori was absent in the H. pylori nikR mutant. A similar lack of nickel responsiveness was observed upon removal of a 19-bp palindromic sequence in the ureA promoter, as demonstrated by using a genomic ureA::lacZ reporter gene fusion. In conclusion, the H. pylori NikR protein and a 19-bp operator sequence in the ureA promoter are both essential for nickel-responsive induction of urease expression in H. pylori.
authors: Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands. vanvliet@mdl.azr.nl
authors: Arnoud H M
authors: AH
authors: van Vliet
authors: Sophie W
authors: SW
authors: Poppelaars
authors: Beverly J
authors: BJ
authors: Davies
authors: Jeroen
authors: J
authors: Stoof
authors: Stefan
authors: S
authors: Bereswill
authors: Manfred
authors: M
authors: Kist
authors: Charles W
authors: CW
authors: Penn
authors: Ernst J
authors: EJ
authors: Kuipers
authors: Johannes G
authors: JG
authors: Kusters
mesh_terms: D001483:Base Sequence; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009532:Nickel / Q000494:pharmacology*; D009875:Operator Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014510:Urease / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C402409:NikR protein, E coli; D012097:Repressor Proteins; D009532:Nickel; D014510:Urease