Bacterial Pathogenesis, Molecular Basis of
that consist of carbohydrate are generally
components of the bacterial cell mem-
brane, wall, or an exopolysaccharide coat-
ing known as the capsule. Many organisms
are believed to use a two-step process in
which an initial loose binding is medi-
ated by adhesins such as pili followed by a
tighter binding owing to the action of other
adhesins. This demonstrates that it is com-
mon for a single pathogen to synthesize
and utilize more than one adhesin.
The function of an adhesin implies the
presence of a receptor for that adhesin.
The variety of molecules that can be used
as receptors include proteins of the host
cell membrane, glycolipids, glycoproteins,
and proteins that make up the extracellular
matrix such as Fbronectin and collagen. In
some cases, the pathogen can even inject
its own receptor into the host, have it
located to the surface, and then use it
to bind to the host cell. This appears to be
the mechanism used by enteropathogenic
E. coli
The best-understood adherence mech-
anism is the use of protein structures
known as Fmbriae or pili. These rodlike
structures are composed of protein sub-
units termed
, which are arrayed and
extend outward from the surface of the
pathogen. In some organisms, the pili are
distributed over the entire surface, while in
others the pili are localized to a preferen-
tial location on the surface. In some cases,
the tip of the pilus mediates the actual
adherence. This is accomplished by a very
speciFc binding of the pilus to a molecule
on the host cell surface. The host cell recep-
tors are most often carbohydrate residues
that are part of glycoprotein or glycolipid
molecules. The speciFcity of the bind-
ing to these host receptors is signiFcant
in determining where, within the body,
the organism will eventually bind, since
some receptors may be tissue-speciFc. In
some cases, the speciFcity of binding is
determined by a special tip structure that
consists of several proteins different from
pilin. In others, it appears that pilin itself
is involved.
The synthesis and assembly of pili is
a complex process that requires proteins
other that those involved in the actual
pilus structure itself. Usually, the tip of
the pilus is assembled and secreted into
the periplasm, where specialized proteins
known as chaperones hold the pilus
proteins in the proper conformation for
the addition of further pilin subunits and
the eventual transport of the growing pilus
to the outer membrane. Pilin subunits are
added to the base of the pilus molecule
until the proper length is reached. The
signals involved in determining the proper
length of the pilus are not understood.
It is known that a periplasmic protein is
involved in signaling for the end of pilus
synthesis, but the mechanism by which it
conveys this information is still a mystery.
There are numerous families of pili that
use diverse mechanisms of biogenesis and
that have distinct structural characteristics.
Attachment is especially important in
areas such as the mouth, the intestinal
tract, and the bladder, which are washed
by fluids. In these areas, only organisms
capable of adhering will be capable of
persisting. One of the most obvious of
these sites is the urinary tract, which is
subject to washing by urine. A number
of the adhesins of uropathogenic
E. coli
strains have been identiFed and studied.
Several pilus types have been identiFed.
The type 1 pili appear to be involved in the
colonization of the vaginal tract; however,
the contribution of these pili in bladder
infections appears to be minimal. The P
pili, synthesized by the products of the
ili) genes,
are extremely important in strains that
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