title: A mutation in the Bordetella bronchiseptica bvgS gene results in reduced virulence and increased resistance to starvation, and identifies a new class of Bvg-regulated antigens.
abstract: The Bordetella BvgAS signal-transduction system has traditionally been viewed as mediating a transition between two distinct phenotypic phases: the Bvg+ phase, characterized by the expression of adhesins and toxins, and the Bvg-phase, characterized by motility in Bordetella bronchiseptica and by the expression of vrg loci in Bordetella pertussis. In B. bronchiseptica, the Bvg+ phase is necessary and sufficient for respiratory tract colonization whereas the Bvg phase is required for growth under nutrient-limiting conditions. This report describes the characterization of a mutant that is locked in a Bvg-intermediate (Bvg[i]) phase. The mutation conferring this phenotype, designated bvgS-I1, results in a threonine-to-methionine substitution near the primary site of phosphorylation in BvgS. Compared to its Bvg+-phase-locked parent, the Bvg(i) mutant displays increased resistance to nutrient limitation and reduced virulence. Molecular analyses indicate that the mutant has lost the ability to express a subset of Bvg+-phase factors and has gained the ability to express factors unique to the Bvg(i) phase. Although identified by mutation, this work indicates that the Bvg(i) phase is expressed by wild-type B. bronchiseptica in response to certain (semi-modulating) environmental conditions. The identification of Bvg(i)-specific antigens suggests the existence of a new class of Bvg-regulated genes. We hypothesize that BvgAS is capable of mediating the expression of a spectrum of phenotypic phases in response to the various environments encountered as Bordetella travels within and between mammalian hosts.
authors.affiliation: Department of Microbiology and Immunology, UCLA School of Medicine, University of California, Los Angeles 90095-1747, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Cotter
authors.forename: J F
authors.initials: JF
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D016950:Bordetella bronchiseptica / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D009525:Niacin / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D012329:RNA, Bacterial; D014157:Transcription Factors; C080662:bvgS protein, Bordetella pertussis; D009525:Niacin