title: A novel nickel responsive MerR-like regulator, NimR, from Haemophilus influenzae.
abstract: We have identified a novel regulator from the MerR family of transcription factors in the bacterial pathogen Haemophilus influenzae (HI1623; nickel-associated merR-like Regulator--NimR). NimR regulates the expression of a Ni(2+) uptake transporter (NikKLMQO). The promoters for nimR and the nik operon are divergent and overlapping and NimR binds at a site between the promoter elements for nikKLMQO. Expression of this operon requires NimR and depends on Ni(2+). Growth rates of the H. influenzae nimR and nikQ mutants were reduced in chemically defined media compared to the wild type and the mutants were unable to grow in the presence of EDTA. The mutant strains were less tolerant of acidic pH and the wild type Rd KW20 could not tolerate low pH in the presence of fluoramide, a urease specific inhibitor, confirming that both nickel transport and urea hydrolysis are a central process in pH control. H. influenzae nimR and nikQ strains were deficient in urease activity, but this could be specifically restored by the addition of excess Ni(2+). NimR did not directly regulate the expression of urease genes but the activity of urease requires both nimR and nikQ. Purified NimR is a dimer that binds 1 Ni(2+)ion. NimR is the first example of a Ni-dependent regulator from the MerR family and targeting a metal ion uptake system; it is distinct from NikR the Ni-responsive regulators of the ribbon-helix-helix family.
authors.affiliation: School of Molecular and Biomedical Science, The University of Adelaide, North Terrace Campus, Adelaide, South Australia 5005, Australia.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Kidd
authors.forename: Karrera Y
authors.initials: KY
authors.lastname: Djoko
authors.forename: JiaQi
authors.initials: J
authors.lastname: Ng
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Argente
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D006193:Haemophilus influenzae / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009532:Nickel / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014510:Urease / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D014157:Transcription Factors; D009532:Nickel; D014510:Urease