Diversity in the Bordetella virulence regulon: transcriptional control of a Bvg-intermediate phase gene

The BvgAS signal transduction system controls the expression of at least th ree distinct phenotypic phases that lie along a continuum of gene expressio n states. The Bvg(+) phase is characterized by the expression of adhesins a nd toxins, whereas the Bvg(-) phase is characterized by motility in Bordete lla bronchiseptica and the expression of vrg loci in Bordetella pertussis. The Bvg-intermediate (Bvg(i)) phase is characterized by the absence of Bvg- repressed phenotypes, the expression of some, but not all, Bvg-activated vi rulence factors and the presence of a recently discovered set of antigens a nd phenotypes that are unique to this phase. We report here the transcripti onal regulation of bipA, the first-identified Bvg(i) phase gene. We have ma pped the bipA promoter and identified numerous BvgA binding sites in the tr anscriptional control region. Based on these data, we present a model in wh ich phase-dependent expression of bipA results from the spatial distributio n and relative affinities of multiple BvgA binding sites relative to the st art site of transcription.