Mechanisms of Bordetella pathogenesis

Bordetella are Gram negative bacteria that cause respiratory tract infections in humans and animals. While at least five different species of Bordetella are known to exist, this review focuses on B. pertussis, B. bronchiseptica and B. parapertussis subspecies. In their virulent phase, all of these bacteria produce a nearly identical set of virulence factors which include adhesins such as filamentous hemagglutinin (FHA), fimbriae and pertactin, as well as toxins such as a bifunctional adenylate cyclase/hemolysin, dermonecrotic toxin, tracheal cytotoxin, a B. pertussis specific pertussis toxin and B. bronchiseptica specific type III secreted proteins. Expression of nearly all of these virulence factors is positively regulated by the products of the bvgAS locus. BvgA and BvgS comprise a two-component signal transduction system that mediates transition between at least three identifiable phases --- a virulent (Bvg(+)) phase, an avirulent (Bvg(-)) phase and an intermediate (Bvg(+)) phase --- in response to specific environmental signals. Bordetella colonize the ciliated respiratory mucosa, a surface designed to eliminate foreign particles, thereby making the adherence and persistence mechanisms of these bacteria crucial. The development of relevant animal models for B. bronchiseptica has enabled us to study Bordetella pathogenesis in the context of natural host-pathogen interactions. In addition, evolutionary studies across the various Bordetella species and detailed analysis of differential regulation of Bvg-activated/repressed genes has greatly enhanced our understanding of the mechanisms of Bordetella pathogenesis.