The BvgAS two-component system of Bordetella pertussis directly activates the expression of a large number of virulence genes in an environmentally responsive manner. The Bvg mode also promotes the expression of the phosphodiesterase BvgR, which turns off the expression of another set of genes, the vrgs, by reducing levels of c-di-GMP. Increased levels of c-di-GMP in the Bvg mode are required, together with the phosphorylated response regulator protein RisA∼P, to activate vrg expression. Phosphorylation of RisA requires RisK, a non-co-operonic sensor kinase, but not its co-operonic sensor kinase RisS which is truncated in B. pertussis but intact in the ancestral B. bronchiseptica. The loss of RisS during evolution of B. pertussis led to the ability to express the vrgs, potentially enhancing aerosol transmission of B. pertussis.
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