Bordetella pertussis produces a complex array of adhesins, aggressins and t
oxins that are presumed to be important in the colonisation of its human ho
st and in ensuring its survival and propagation. The organism also has high
ly sophisticated mechanisms for regulating virulence factor expression, in
response to environmental signals or by reversible mutations. Despite the r
apidly increasing knowledge of these aspects of the biology of B. pertussis
, our understanding of the pathogenesis of whooping cough is still far from
clear. In defining the role of individual factors, reliance has to be plac
ed on in vitro assays or animal models of the human infection, particularly
in the mouse, where different conditions may prevail. Some clues to pathog
enic mechanisms may be provided by considering other bordetellae, especiall
y B. parapertussis, B. bronchiseptica and B. avium, their similar, but not
identical, range of virulence factors and the common features of the diseas
es caused by these species in their respective hosts. The bordetellae are u
sually defined as obligate, non-invasive parasites of the respiratory tract
s of warm-blooded animals, including birds, with a predilection for the res
piratory ciliated epithelium. This definition has been challenged by a numb
er of recent observations. For example, the ability of Bordetella sop. to r
egulate virulence factor expression in response to external signals strongl
y suggests that they have alternative habitats where such regulation would
be an advantage. These habitats may be intracellular, since it has been sho
wn that B. pertussis, B, parapertussis and B. bronchiseptica can invade and
survive within host cells, or they may be in other sites within the same o
r different hosts. Recent DNA fingerprinting studies of B. pertussis have r
evealed hitherto unsuspected heterogeneity amongst isolates which could be
reflected in antigenic differences between strains. Some of these new persp
ectives on Bordetella pathogenicity may have implications for pertussis vac
cine development. (C) 1999 The International Association for Biologicals.