The proline residue at position 319 of BvgS is essential for BvgAS activation in Bordetella pertussis.

Abstract

Bordetella pertussis is the etiological agent of pertussis and produces various virulence factors, including pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), most of which are positively regulated by the BvgAS two-component sensory transduction system. Here, we describe a B. pertussis isolate not expressing PT, FHA and PRN recovered from a pertussis patient. Sequencing revealed that the bvgS gene of this isolate contains a spontaneous mutation (C>A at position 955) causing the proline residue at position 319 of the BvgS protein to be substituted by threonine. Moreover, loss of PT, FHA and PRN expression was completely restored by complementation with a wild-type bvgAS locus, indicating that this non-synonymous substitution in bvgS leads to impaired BvgS function. Our findings indicate that the proline residue at position 319 in this protein plays an essential role in activation of the BvgAS system and, therefore, subsequent expression of Bvg-regulated virulence factors in B. pertussis.