Bacterial Pathogenesis, Molecular Basis of
563
bubonic plague, via direct inoculation in
the form of a bite. The increased use of in-
dwelling medical devices such as catheters
also provides portals of entry into the host
and may actually serve as recurrent sources
of infection. Additional routes of entry
include mucosal surfaces, which are in-
volved in nutrient uptake or gas exchange.
Examples of such surfaces are the gas-
trointestinal and respiratory tracts. These
mucosal surfaces are in constant contact
with the external environment and hence
are under risk of being breached by bac-
teria. These tissues serve as a thin barrier
between the host and the external envi-
ronment and provide a portal of entry for
many bacteria that are capable of invading
a host through intact epithelia. The breach
of the skin barrier is important because
it allows not only the normal flora on the
surface to enter but also invites invasion by
pathogens. Indeed, organisms that are rel-
atively innocuous on the surface of the skin
may actually present problems if allowed to
penetrate the skin barrier and gain access
to underlying tissue or blood vessels.
Some organisms do not directly enter
the host nor require a living vector system
to cause disease. Although they can also
cause wound infections, members of the
genus
Clostridium
can elaborate toxins in
foodstuffs that can result in severe disease
upon ingestion. One of the most common
examples of disease without colonization is
botulism.
Clostridium botulinum
is able to
produce botulinum toxin that essentially
acts as a neurotoxin. Upon ingestion of
tainted food, the toxin is absorbed from
the intestines into the circulation and
binds to susceptible neurons. Part of the
toxin (i.e. the light chain) is internalized
in the cytoplasm of the neurons where
it begins to exert its proteolytic activity
and disrupt cellular pathways required
for the release of chemical messenger
molecules. As a result, the muscles do not
receive the proper signals and essentially
enter a state of flaccid paralysis. As
the paralysis progresses further, there
is risk of fatal respiratory and cardiac
failure.
5.3
Adherence to Host Cells
Once inside a host, bacterial pathogens can
adhere either directly to a host cell surface
or to a component of the extracellular
matrix, which functions as a foundation
for the host cells. Some pathogens remain
on the surface of a cell and multiply at that
location, while others make use of their
ability to invade the tissue in search of a
more suitable location. Nonetheless, even
invasive organisms must initially attach
to a host cell. This is a key step in the
interaction between the pathogen and the
host. Implicit in this interaction is that
the organism must possess a molecule
that can allow it to adhere to a host and
that the host must possess a receptor
for the bacterial adhesin. The surfaces of
attachment can be the skin, the mucosal
membranes, and some of the deeper
tissues. The host has evolved mechanisms
such as coughing, sneezing, secretion of
saliva, and mucus flow in an attempt to
wash away the bacteria. However, some
pathogens are able to strongly attach
themselves and prevent their eradication
from the host. These organisms utilize
speciFc components, termed
adhesins
,to
adhere themselves to receptor sites on the
host cell surfaces.
The types of adhesins used by bacte-
rial pathogens are varied. They may be
composed of either proteins or carbohy-
drates. The protein adhesins are generally
separated into two groups known as Fm-
brial (pili) and aFmbrial. Those adhesins
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