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

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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 (Bvgi) 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 Bvgi 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 Bvgi phase. Although identified by mutation, this work indicates that the Bvgi phase is expressed by wild‐type B. bronchiseptica in response to certain (semi‐modulating) environmental conditions. The identification of Bvgi‐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.

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