566
Bacterial Pathogenesis, Molecular Basis of
Even though both these molecules have
a high degree of homology at the amino
acid level, they appear to bind two different
receptors. S2 speciFcally binds to a glycol-
ipid called
lactosylceramide
,whichisfound
primarily on ciliated respiratory cells. S3
binds to a ganglioside found primarily on
phagocytic cells. It should be noted that
±ha can also bind CR3 on polymorphonu-
clear monocytes.
Bordetella pertussis
also
produces pili and a surface protein known
as pertactin.
Some organisms use polysaccharide-
based adhesins to attach to host tissue.
These adhesins are exempliFed by the
teichoic acids (components of the gram-
positive bacterial cell wall), lipopolysaccha-
rides or lipooligosaccharides (found only
in gram-negative organisms), or capsules
(found on both gram-positive and negative
organisms). As examples, both
Staphylo-
coccus
and
Streptococcus spp
. utilize their
teichoic acids as adhesins;
Haemophilius
influenzae
makes use of lipooligosaccha-
rides to attach to respiratory epithelial
cells; and adhesion of
Mycobacterium spp.
is promoted by the glucan and mannan
polysaccharides found in their capsule.
A little-discussed facet of adherence is
the role that the host cell itself may play in
aiding the attachment of the pathogen. It
is known that interactions with pathogens
activate various host cell–signaling sys-
tems. Recent data suggest that pathogens
may be able to connect to these signaling
mechanisms to encourage the host cell to
synthesize receptors to facilitate bacterial
adherence. Recent data suggest that vari-
ous enteropathogenic
E. coli
may secrete
proteins that stimulate the expression of
speciFc receptors on host cell surfaces.
The
E. coli
then utilizes these receptors for
adherence.
Streptococcus pneumoniae
has
also been shown to stimulate host cells to
express a receptor for its adherence.
5.4
Evasion of the Host Immune Response
After attachment, the bacteria must sur-
vive in their new environment. Toward
this end, the bacteria must compete for
nutrients not only with the host but also
with the indigenous microbial flora. In ad-
dition, the organism must be able to evade
the components of the host immune re-
sponse. Antibodies and complement are
the major components of the humoral re-
sponse and when these proteins encounter
a pathogenic organism or its soluble com-
ponents, the antibodies bind to form an
antibody–antigen complex. In the case of
whole organisms, a series of complement
proteins bind the complex and result in
the lysis and death of the pathogen. Some
pathogens (e.g.
S. typhimurium
) exhibit
serum resistance in that they are able to
inhibit the formation of the complement
complex and thereby avoid cell lysis. In
the case of soluble factors, the formation
of the complex makes it easy to phago-
cytize and remove pathogens by speciFc
cells. However, the formation of the im-
mune complexes themselves may cause
pathology as seen in complex-mediated
hypersensitivity in which the host im-
mune system is turned against the host
itself. An excellent example is the case
of post-
Streptococcal
glomerulonephritis.
The classic view of this disease postu-
lates that lysis products of
Streptococcus
pyogenes
that result from the host inflam-
matory response attempting to clear a
throat infection eventually enter the blood-
stream and initiate an antibody response.
The high levels of antibodies produced
by the host then interact with antigens
present in the bloodstream, resulting in
the formation of antibody–antigen com-
plexes, which may then accumulate in the
kidney. The complexes themselves may
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