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The whooping cough agent  Bordetella pertussis  regulates the production of its virulence factors by the BvgA/S system. Phosphorylated BvgA activates the virulence-activated genes ( vag s) and represses the expression of the virulence-repressed genes ( vrg s) via the activation of the  bvgR  gene. In modulating conditions, with MgSO 4 , the BvgA/S system is inactive, and the  vrg s are expressed. Here, we show that the expression of almost all  vrg s depends on RisA, another transcriptional regulator. We also show that some  vag s are surprisingly no longer modulated by MgSO 4  in the  risA  −  background. RisA also regulates the expression of other genes, including chemotaxis and flagellar operons, iron-regulated genes, and genes of unknown function, which may or may not be controlled by BvgA/S. We identified RisK as the likely cognate RisA kinase and found that it is important for expression of most, but not all RisA-regulated genes. This was confirmed using the phosphoablative RisAD 60 N and the phosphomimetic RisAD 60 E analogues. Thus the RisA regulon adds a new layer of complexity to  B. pertussis  virulence gene regulation.

The multifaceted RisA regulon of Bordetella pertussis