A new era of research into Bordetella pertussis pathogenesis.

Abstract

The pathogenesis of Bordetella pertussis infection in humans has been succinctly reviewed previously by Hewlett. To summarise, the introduction of B. pertussis into the respiratory tract in droplets is followed by interaction with ciliated epithelial cells, likely to be dependent on bacterial adhesins, of which at least five have been suggested : filamentous haemagglutinin (FHA), pertactin (PRN), fimbriae, pertussis toxin (PT) and tracheal colonization factor. The expression of many of the proteins implicated in Bordetella pathogenesis, including these adhesins, is regulated in response to environmental stimuli by a two-component regulatory system encoded by the bvg genes. It is likely that the expression of members of the bvg regulon is altered dependent on the different environments encountered in the respiratory tract. The next step in pathogenesis is thought to be paralysis of the cilia and death of ciliated cells, probably mediated by a synergistic effect of tracheal cytotoxin (TCT) and lipopolysaccharide (LPS) via induction of interleukin-1 (IL-1) and nitric oxide. This leads to defective mucociliary clearance, allowing the bacteria to establish in, and move down, the respiratory tract. Expression of the bvgregulated toxins, PT and adenylate cyclase-haemolysin, may damage the respiratory tract further and may also interfere with immune responses. PT has been suggested as a primary cause of the prolonged cough associated with pertussis, but this view is difficult to uphold in the face of evidence that infection by B. parapertussis, which apparently does not biosynthesise PT, can also cause cough. At this point the infection is established and the patient exhibits the symptoms characteristic of whooping cough. Depending on the response of the patient the