CHARACTERIZATION OF THE BVGR LOCUS OF BORDETELLA-PERTUSSIS

Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is d ependent upon the bvg locus (originally designated the vir locus), whi ch encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regu lator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expr ession of the aforementioned bvg-activated virulence factors is maxima l; this repression is dependent upon the presence of an intact bvgAS l ocus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, des ignated bvgR, maps to a location immediately downstream of bvgAS. We h ave undertaken deletion and complementation studies, as well as sequen ce analysis, in order to identify the bvgR open reading frame and iden tify the cis-acting sequences required for regulated expression of bvg R. Studies utilizing transcriptional fusions of bvgR to the gene encod ing alkaline phosphatase have demonstrated that bvgR is activated at t he level of transcription and that this activation is dependent upon a n intact bvgAS locus.