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

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-l1, 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.