568
Bacterial Pathogenesis, Molecular Basis of
In actuality, the concept of invasion can
be subcategorized into two types, extra-
cellular and intracellular. In extracellular
invasion, a pathogen breaches the barriers
of various tissues in order to dissemi-
nate within the host but in a manner
in which it does not actually enter the
host cells. Some organisms (e.g.
P. aerug-
inosa
and
Staphylococcus aureus
)p
roduce
and secrete enzymes that degrade host cell
molecules such as elastin, an extracellular
protein, and hyaluronic acid, the cement
that holds cells together. Destruction of
these molecules allows the organism to
move from one location to another more
suitable location where they can survive
and proliferate.
Many pathogens, both gram-positive and
gram-negative, have the ability to invade
intracellularly. In fact, some pathogens
such as
Chlamydia spp.
and
Rickettsia spp.
are obligate intracellular pathogens and
absolutely require a host cell for growth.
Other pathogens are classiFed as faculta-
tively intracellular and invade host cells to
proliferate or to spread to other tissues.
The advantage of intracellular invasion is
several-fold. ±irst, it sequesters the organ-
ism from the potentially lethal effects of
the host immune system. Second, it places
the organism in an environment that is
nutrient-rich. Lastly, it positions the or-
ganism in a location where competition
from other organisms is almost nonexis-
tent. However, invasion requires a set of
complex biological mechanisms that must
allow the organism a means to not only
enter the cells but also survive, multiply,
and eventually disseminate from the tar-
get tissue. Intracellular invasion can also
be subdivided into two types. There are
those pathogens that take advantage of the
ability of highly differentiated professional
phagocytes, which normally ingest bacte-
ria. Other pathogens are able to invade cells
that do not have the ability to ingest bac-
teria. In this type of invasion, the process
is considered directed. That is, the bac-
terium directs the production of various
factors known as invasins or internalins
that allow the organism to invade. One
example of such a pathogen is
Y. pseudotu-
berculosis
.Th
isorgan
ismu
t
i
l
izesinvas
ins
including the Inv and YadA products to
associate with the
β
1-integrin on the host
cell surface. The association with multiple
receptors leads to the bacterium becom-
ing literally enveloped by the host cell and
thus internalized. The process has some-
times been referred to as a
zippering
on the
basis of the obvious structural analogies
as the host cell surrounds the bacterium.
In contrast,
Shigella spp.
,wh
i
cha
rea
l
so
intestinal pathogens, utilize a different ap-
proach involving the temperature-sensitive
induction of Mxi–Spa and Ipa products.
Immediately following ingestion, the cells
begin to synthesize the Mxi, Spa, and Ipa
products owing to the temperature of the
host. The Mxi–Spa products assemble in
the membranes of the organism and form
a translocation apparatus that is used to
move the Ipa proteins out of the cell once
contact with the host cell has been made.
The Ipa proteins form complexes that in-
teract with the host cell surface and alter
the signaling pathways of the host cell.
The altered signaling results in rearrange-
ments of the host cell cytoskeleton and
leads to the formation of membrane pro-
jections giving the host cell a ‘‘ruffled’’
appearance. Eventually, the projections of
th
em
emb
r
an
een
c
i
r
c
l
eth
e
Shigella
and
the organism is taken into the cytoplasm
of the host cell. It should be noted that
some pathogens make use of both extra-
cellular and intracellular mechanisms of
invasion in order to proliferate.
Onceinsideacell,thereareanumberof
possible outcomes for the pathogen. The
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