title: Heme-responsive transcriptional activation of Bordetella bhu genes.
abstract: Bordetella pertussis and Bordetella bronchiseptica, gram-negative respiratory pathogens of mammals, possess a heme iron utilization system encoded by the bhuRSTUV genes. Preliminary evidence suggested that expression of the BhuR heme receptor was stimulated by the presence of heme under iron-limiting conditions. The hurIR (heme uptake regulator) genes were previously identified upstream of the bhuRSTUV gene cluster and are predicted to encode homologs of members of the iron starvation subfamily of extracytoplasmic function (ECF) regulators. In this study, B. pertussis and B. bronchiseptica DeltahurI mutants, predicted to lack an ECF sigma factor, were constructed and found to be deficient in the utilization of hemin and hemoglobin. Genetic complementation of DeltahurI strains with plasmid-borne hurI restored wild-type levels of heme utilization. B. bronchiseptica DeltahurI mutant BRM23 was defective in heme-responsive production of the BhuR heme receptor; hurI in trans restored heme-inducible BhuR expression to the mutant and resulted in BhuR overproduction. Transcriptional analyses with bhuR-lacZ fusion plasmids confirmed that bhuR transcription was activated in iron-starved cells in response to heme compounds. Heme-responsive bhuR transcription was not observed in mutant BRM23, indicating that hurI is required for positive regulation of bhu gene expression. Furthermore, bhuR was required for heme-inducible bhu gene activation, supporting the hypothesis that positive regulation of bhuRSTUV occurs by a surface signaling mechanism involving the heme-iron receptor BhuR.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, 420 Delaware Street S.E., Minneapolis, MN 55455-0312, USA.
authors.forename: Carin K
authors.initials: CK
authors.lastname: Vanderpool
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Armstrong
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D001884:Bordetella / Q000235:genetics*; D003470:Culture Media; D005798:Genes, Bacterial / Q000502:physiology*; D006418:Heme / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D011956:Receptors, Cell Surface; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; C431916:BhuR protein, Bordetella pertussis; D003470:Culture Media; D011956:Receptors, Cell Surface; D006418:Heme; D007501:Iron