title: Expression of hurP, a gene encoding a prospective site 2 protease, is essential for heme-dependent induction of bhuR in Bordetella bronchiseptica.
abstract: Expression of the hurIR bhuRSTUV heme utilization locus in Bordetella bronchiseptica is coordinately controlled by the global iron-dependent regulator Fur and the extracytoplasmic function sigma factor HurI. Activation of HurI requires transduction of a heme-dependent signal via HurI, HurR, and BhuR, a three-component heme-dependent regulatory system. In silico searches of the B. bronchiseptica genome to identify other genes that encode additional participants in this heme-dependent regulatory cascade revealed hurP, an open reading frame encoding a polypeptide with homology to (i) RseP, a site 2 protease (S2P) of Escherichia coli required for modifying the cytoplasmic membrane protein RseA, and (ii) YaeL, an S2P of Vibrio cholerae required for modification of the cytoplasmic membrane protein TcpP. A mutant of B. bronchiseptica defective for hurP was incapable of regulating expression of BhuR in a heme-dependent manner. Furthermore, the hurP mutant was unable to utilize hemin as a sole source of nutrient Fe. These defects in hemin utilization and heme-dependent induction of BhuR were restored when recombinant hurP (or recombinant rseP) was introduced into the mutant. Introduction of hurP into a yaeL mutant of V. cholerae also complemented its S2P defect. These data provided strong evidence that protease activity and cleavage site recognition was conserved in HurP, RseP, and YaeL. The data are consistent with a model in which HurP functionally modifies HurR, a sigma factor regulator that is essential for heme-dependent induction of bhuR.
authors.affiliation: The Witebsky Center for Microbial Pathogenesis and Immunology and the Department of Microbiology and Immunology, The University at Buffalo, 3435 Main St., Buffalo, NY 14221, USA.
authors.forename: Natalie D
authors.initials: ND
authors.lastname: King-Lyons
authors.forename: Kelsy F
authors.initials: KF
authors.lastname: Smith
authors.forename: Terry D
authors.initials: TD
authors.lastname: Connell
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis*; D016950:Bordetella bronchiseptica / Q000235:genetics* / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006418:Heme / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010447:Peptide Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D016415:Sequence Alignment; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C028027:heme receptor; D006418:Heme; D006427:Hemin; D007501:Iron; D010450:Endopeptidases; D010447:Peptide Hydrolases; C440001:RseP protein, E coli