title: Hierarchical regulation of the NikR-mediated nickel response in Helicobacter pylori.
abstract: Nickel is an essential metal for Helicobacter pylori, as it is the co-factor of two enzymes crucial for colonization, urease and hydrogenase. Nickel is taken up by specific transporters and its intracellular homeostasis depends on nickel-binding proteins to avoid toxicity. Nickel trafficking is controlled by the Ni(II)-dependent transcriptional regulator NikR. In contrast to other NikR proteins, NikR from H. pylori is a pleiotropic regulator that depending on the target gene acts as an activator or a repressor. We systematically quantified the in vivo Ni(2+)-NikR response of 11 direct NikR targets that encode functions related to nickel metabolism, four activated and seven repressed genes. Among these, four targets were characterized for the first time (hpn, hpn-like, hydA and hspA) and NikR binding to their promoter regions was demonstrated by electrophoretic mobility shift assays. We found that NikR-dependent repression was generally set up at higher nickel concentrations than activation. Kinetics of the regulation revealed a gradual and temporal NikR-mediated response to nickel where activation of nickel-protection mechanisms takes place before repression of nickel uptake. Our in vivo study demonstrates, for the first time, a chronological hierarchy in the NikR-dependent transcriptional response to nickel that is coherent with the control of nickel homeostasis in H. pylori.
authors.affiliation: Département de Microbiologie, Institut Pasteur, Unité Pathogenèse de Helicobacter, Paris Cedex 15, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Muller
authors.forename: Christelle
authors.initials: C
authors.lastname: Bahlawane
authors.forename: Sylvie
authors.initials: S
authors.lastname: Aubert
authors.forename: Catherine Marie
authors.initials: CM
authors.lastname: Delay
authors.forename: Kristine
authors.initials: K
authors.lastname: Schauer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Michaud-Soret
authors.forename: Hilde
authors.initials: H
authors.lastname: De Reuse
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D009532:Nickel / Q000494:pharmacology*; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; C523724:NikR protein, Helicobacter pylori; D012097:Repressor Proteins; D009532:Nickel