(A) The BvgAS phosphorelay.

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(A) The BvgAS phosphorelay. (A) The BvgAS phosphorelay. BvgS is a transmembrane sensor protein consisting of a periplasmic domain (P), a linker region (L), and histidine kinase (HPK), receiver (R), and histidine phosphotransfer domains (HPD). BvgA is a response regulator that contains receiver (R) and helix-turn-helix (HTH) domains. Under inducing signals, BvgS autophosphorylates and initiates a phosphorelay that eventually leads to the phosphorylation and activation of BvgA. The sequential steps in the phosphorelay and the amino acid residues involved are shown. The bvgS-C3 allele confers constitutive activity. BvgAS controls as least three distinct phenotypic phases in response to environmental conditions. The Bvg+ phase or X mode is necessary and sufficient for respiratory tract colonization and is associated with the expression of virulence factors. The Bvgi phase is hypothesized to be important for respiratory transmission and is characterized by the expression of a subset of Bvg+ phase-specific factors as well as factors expressed maximally in the Bvgi phase. B. pertussis and B. bronchiseptica express a significantly different array of proteins in their Bvg− phase. The Bvg− phase of B. bronchiseptica is necessary and sufficient for growth under nutrient-limiting conditions and is predicted to play a role in survival in the environment. Other abbreviations: om, outer membrane; cm, cell membrane. (B) Expression curves for the four classes of genes regulated by BvgAS. Genes expressed maximally in the Bvg+ phase (such as cyaA) are referred to as “late” Bvg-activated genes and are represented by the black curve (curve 1). Genes that are expressed maximally under both Bvg+ and Bvgi phase conditions (such as fhaB) are referred to as “early” Bvg-activated genes and are represented by the green curve (curve 2). Genes expressed maximally only under Bvgi phase conditions (such as bipA) are represented by the gold curve (curve 3). Finally, genes that are repressed by BvgAS and expressed maximally only under Bvg− phase conditions are represented by the red curve (curve 4). Abbreviation: nic, nicotinic acid. Seema Mattoo, and James D. Cherry Clin. Microbiol. Rev. 2005; doi:10.1128/CMR.18.2.326-382.2005