title: Molecular characterization of the BvgA response regulator of Bordetella holmesii.
abstract: The BvgAS system controls the expression of most virulence factors in Bordetella pertussis. Recently, we identified an orthologous system in the related human pathogen Bordetella holmesii. However, while we found that the orthologous histidine kinases BvgS could be functionally exchanged between the two species, the B. holmesii response regulator BvgA(BH) could not substitute for its B. pertussis counterpart in vivo and, accordingly, was not able to bind to B. pertussis virulence promoters in vitro. Here we show that a hybrid response regulator consisting of the B. pertussis derived DNA-binding output domain of BvgA(BP) combined with the B. holmesii receiver domain binds to BvgA(BP) regulated virulence promoters of B. pertussis in vitro and is functional in B. pertussis in vivo. This shows that the inability of BvgA(BH) to complement BvgA(BP) in B. pertussis is due to the small number of sequence variations present in its output domain. However, by mutation analysis we show that four amino acid exchanges present in the helix-turn-helix motif of BvgA(BH) as compared to BvgA(BP) are not the only reason for its inability to substitute for BvgA(BP) but additional mutations present in the output domain must play a role.
authors.affiliation: Lehrstuhl für Mikrobiologie, Biozentrum, Universität Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Horvat
authors.forename: Roy
authors.initials: R
authors.lastname: Gross
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001884:Bordetella / Q000235:genetics / Q000502:physiology*; D001886:Bordetella pertussis / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; C065601:BvgA protein, Bacteria; D011994:Recombinant Proteins; D014157:Transcription Factors; D037521:Virulence Factors