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.