The gram-negative bacterium Bordetella pertussis is the causative agent of pertussis, or whooping cough. The organism was first isolated from a patient and implicated as the cause of the disease in the early 1900s. A killed, whole cell vaccine developed soon thereafter proved efficacious in controlling the disease and remains in use today. Recently, however, concern over adverse reactions to the vaccine has led to lower vaccine acceptance and debate about its continued use. As a consequence, development of a less reactogenic preparation has become a top priority. One of the important considerations in the design of a new vaccine is the pathophysiology of pertussis; identification of individual virulence factors and assessment of their roles in the disease will provide a sound basis for vaccine development, which has had a very empirical basis in the past. B. pertussis has the ability to inhibit the function of the host's immune system. The toxin, known as pertussis toxin (or PTx), inhibits G protein coupling that regulates an adenylate cyclase-mediated conversion of ATP to cyclic AMP.
Pertussis toxin is the most extensively studied product of B. pertussis and is undoubtedly a major virulence factor. The toxin has previously been known by a number of names, many referring to the biological consequences of its actions in vivo: e.g. histamine-sensitizing factor, lymphocytosis-promoting factor, islet-activating protein and pertussigen. Figure 1 shows the schematic model of the Pertussis toxin of B. Pertussis:
Fig. 1 the 3D structure of the Pertussis Toxin
Bordetella pertussis organisms undergo a phase variation characterized by simultaneous loss of the expression of multiple virulence factors. Study of this process and the specific bacterial products absent in phase variants provides a view of virulence factors from the perspective of the pathogen. Spontaneous variants that are no longer able to cause disease in animal models occur at a frequency of one per 103-106 organisms. A virulent phase mutants revert back to virulent phase at a low frequency.