To search the entire book, enter a term or phrase in the form below
Bordetella pertussis and Whooping Cough (page 1)
(This chapter has 3 pages)
© Kenneth Todar, PhD
the agent of pertussis or whooping cough. Gram stain. (CDC)
Whooping cough (pertussis) is caused by the bacterium Bordetella
pertussis. B. pertussis is a very small
aerobic coccobacillus that appears singly or in pairs. Its metabolism
respiratory, never fermentative, and taxonomically, Bordetella
placed among the "Gram-negative Aerobic Rods and Cocci" in Bergey's
is not assigned to any family. The bacteria are nutritionally
and are usually cultivated on rich media supplemented with blood. They
can be grown in synthetic medium, however, which contains buffer,
an amino acid energy source, and growth factors such as nicotinamide
which there is a strict requirement). Even on blood agar the organism
slowly and requires 3-6 days to form pinpoint colonies.
Bordetella pertussis colonizes the cilia of the mammalian
epithelium (Figure 1). Generally, it is thought that B. pertussis
does not invade the tissues, but some recent work has shown the
in alveolar macrophages. The bacterium is a pathogen for humans and
for higher primates, and no other reservoir is known. Whooping cough is
a relatively mild disease in adults but has a significant mortality
in infants. Until immunization was introduced in the 1930s, whooping
was one of the most frequent and severe diseases of infants in the
The disease pertussis has two stages. The first stage, colonization, is
an upper respiratory disease with fever, malaise and coughing, which
in intensity over about a 10-day period. During this stage the organism
can be recovered in large numbers from pharyngeal cultures, and the
and duration of the disease can be reduced by antimicrobial treatment.
Adherence mechanisms of B. pertussis involve a "filamentous
(FHA), which is a fimbrial-like structure on the bacterial surface, and
pertussis toxin (PTx). Short range effects of soluble toxins
play a role as well in invasion during the colonization stage.
1. Colonization of tracheal
epithelial cells by Bordetella pertussis
The second or toxemic stage of pertussis follows relatively
symptoms of the colonizaton stage. It begins gradually with prolonged
paroxysmal coughing that often ends in a characteristic inspiratory
(whoop). To hear the characteristic sound of whooping cough click whoop.wav (whoop.wav is copyright of Dr Doug
Jenkinson, Nottingham, England. www.whoopingcough.net). During the
second stage, B. pertussis can rarely be recovered,
and antimicrobial agents have no effect on the progress of the disease.
As described below, this stage is mediated by a variety of soluble
Studies of B. pertussis and its adhesins have focused on
mammalian cells that lack most of the features of ciliated epithelial
However, some generalities have been drawn. The two most important
factors are the filamentous hemagglutinin (FHA) and the pertussis toxin
(PTx). Filamentous hemagglutinin is a large (220 kDa) protein that
filamentous structures on the cell surface. FHA binds to galactose
on a sulfated glycolipid called sulfatide which is very common on the
of ciliated cells. Mutations in the FHA structural gene reduce the
of the organism to colonize, and antibodies against FHA provide
against infection. However, it is unlikely that FHA is the only adhesin
involved in colonization. The structural gene for FHA has been cloned
expressed in E. coli, raising the possibility of its production
for use in a component vaccine.
One of the toxins of B. pertussis, the pertussis toxin
is also involved in adherence to the tracheal epithelium. Pertussis
is a 105 kDa protein composed of six subunits: S1, S2, S3, (2)S4, and
The toxin is both secreted into the extracellular fluid and cell bound.
Some components of the cell-bound toxin (S2 and S3) function as
and appear to bind the bacteria to host cells. S2 and S3 utilize
receptors on host cells. S2 binds specifically to a glycolipid called
which is found primarily on the ciliated epithelial cells. S3 binds to
a glycoprotein found mainly on phagocytic cells.
The S1 subunit of pertussis toxin is the A component with ADP
activity, and the function of S2 and S3 is presumed to be involved in
the intact (extracellular) toxin to its target cell surface. Antibodies
against PTx components prevent colonization of ciliated cells by the
and provide effective protection against infection. Thus, pertussis
is clearly an important virulence factor in the initial colonization
of the infection.
Since the S3 subunit of pertussis toxin is able to bind to the
of phagocytes, and since FHA will attach to integrin CR3 on phagocyte
(the receptor for complement C3b), it has been speculated that the
might bind preferentially to phagocytes in order to facilitate its own
engulfment. The role of such self-initiated phagocytosis is not clear.
Bacteria taken up by this abnormal route may avoid stimulating the
burst that normally accompanies phagocytic uptake of bacterial cells
are opsonized by antibodies or complement C3b. Once inside of cells the
bacteria might utilize other toxins (i.e. adenylate cyclase toxin) to
the bactericidal activities of phagocytes. In any case, there is some
that Bordetella pertussis can use this mechanism to get into
to persist in phagocytes as an intracellular parasite. If B.
is an intracellular parasite it would explain why immunity to pertussis
correlates better with the presence of specific cytotoxic T cells than
it does with the presence of antibodies to bacterial products.
B. pertussis produces at least two other types of adhesins,
types of fimbriae and a nonfimbrial surface protein called pertactin,
their role in adherence and pathogenesis is not well established.