Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in Bordetella.

The two-component system BvgAS of the whooping cough agent Bordetella pertussis regulates the virulence factors necessary for infection in a coordinated manner. BvgS is the prototype of a family of sensor kinase proteins found in major bacterial pathogens. When BvgS functions as a kinase, B. pertussis is virulent, and the bacterium shifts to an avirulent phase after BvgS senses chemicals that make it switch to phosphatase. Our goal is to decipher the signaling mechanisms of BvgS in order to understand virulence regulation in Bordetella, which may lead to new antimicrobial treatments targeting those two-component systems. We discovered that the activity of BvgS is regulated in a mechanical manner. A short region of the protein that precedes the enzymatic domain switches between two states in response to signal perception by other BvgS domains. This switch region is conserved among BvgS homologs, and thus, the regulation uncovered here will likely be relevant for the family.