Bacterial Pathogenesis, Molecular Basis of
557
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given infection site. There is competition
for nutrients and adherence sites, and
many microbes considered part of the
normal flora are able to defend their
territory via the production of various
proteases, toxins, and other deleterious
factors. If a bacterium can survive this
challenge, it must then face the formidable
challenge of trying to evade the human
immune system.
Clearly, in order to survive, a pathogen
must
be able
to
respond and adapt
to its changing environment. Pathogens
must adapt to changes induced during
transmission to a new host or to changes
that occur in the new host as a result of the
pathogens’ presence. The fact that many
successful pathogens have been identiFed
is a testament to the adaptability and
diversity of these organisms. The concept
of adaptability raises the point that we must
recognize that pathogenic bacteria do not
cause disease with malicious intent as is
so often implicitly conveyed in any such
discussion. Rather, they cause disease as
a consequence of the evolutionary stresses
that select for those organisms that can
survive in an environment that is most
often very different from the environment
in which they are usually found. As will
become evident, the balance between host
and pathogen is quite delicate and a small
shift in this balance can give one or the
other the upper hand.
3
What Makes a Pathogen a Pathogen?
Bacteria cover and colonize most of the
exterior surface of the body including
mucosal surfaces. While the majority of
these organisms usually serve a beneFcial
role to the host, or at least do not ap-
pear to be detrimental, a small percentage
of bacteria are pathogenic. This demon-
strates that the association of pathogen
and host does not always lead to disease.
In fact, some pathogens such as
Strepto-
coccus pneumoniae
areab
letoco
lonizethe
host in large numbers; yet the host does
not exhibit signs of streptococcal pneu-
monia. The number of organisms needed
to be present to prove sufFcient to cause
disease is termed an
infectious dose
.The
speciFc infectious dose can vary between
organisms and even for the same organ-
ism in different hosts. Some pathogens
are considered ‘‘overt’’ in that they can
cause disease even in immunocompetent
individuals. Other pathogens are consid-
ered ‘‘opportunistic,’’ causing infection
only when some predisposing factor is
present in the host. A classic example of
an opportunist is
Pseudomonas aeruginosa
,
which infects individuals who have been
immunocompromised in some way.
The Fnding that a small percentage
of organisms can actually be pathogenic
leads us to the question of what makes
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of molecular biology and advances in
geneticsallowedustogainanappreciation
for the complexity of the answer to this
question. Clearly, the susceptibility of the
host plays a large role in the success of a
pathogen, and there is evidence (discussed
further in this chapter) that speciFc genetic
traits of the host may predispose an
individual to a given infection. Just as
clear is the fact that the genetic makeup
of the bacterium itself plays an equally
important role. Closely related bacteria
can demonstrate dramatically different
pathogenic potential. This is evident with
the identiFcation of speciFc strains of
organisms that are pathogenic, while other
strains of the same organism are not.
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