Mechanisms of Bordetella pathogenesis

Bordetella are Gram negative bacteria that cause respiratory tract infectio ns in humans and animals. While at least five different species of Bordetel la are known to exist, this review focuses on B. pertussis, B. bronchisepti ca and B. parapertussis subspecies. In their virulent phase, all of these b acteria produce a nearly identical set of virulence factors which include a dhesins such as filamentous hemagglutinin (FHA), fimbriae and pertactin, as well as toxins such as a bifunctional adenylate cyclase/hemolysin, dermone crotic toxin, tracheal cytotoxin, a B. pertussis specific pertussis toxin a nd B. bronchiseptica specific type III secreted proteins. Expression of nea rly all of these virulence factors is positively regulated by the products of the bvgAS locus. BvgA and BvgS comprise a two-component signal transduct ion system that mediates transition between at least three identifiable pha ses --- a virulent (Bvg(+)) phase, an avirulent (Bvg(-)) phase and an inter mediate (Bvg(+)) phase --- in response to specific environmental signals. B ordetella colonize the ciliated respiratory mucosa, a surface designed to e liminate foreign particles, thereby making the adherence and persistence me chanisms of these bacteria crucial. The development of relevant animal mode ls for B. bronchiseptica has enabled us to study Bordetella pathogenesis in the context of natural host-pathogen interactions. In addition, evolutiona ry studies across the various Bordetella species and detailed analysis of d ifferential regulation of Bvg-activated/repressed genes has greatly enhance d our understanding of the mechanisms of Bordetella pathogenesis.