Bacterial Pathogenesis, Molecular Basis of
555
1
Introduction
Despite tremendous advances in medicine
and public health measures, infectious dis-
eases caused by microbial agents are still
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tality worldwide. This is due not only to
the emergence of new infectious agents
but also to the reemergence of diseases
once thought to be under control. Further-
more, increasing numbers of organisms
resistant to numerous antimicrobials are
being isolated and identi±ed. Organisms
capable of causing disease are referred
to as pathogens and may be generally di-
vided into three main categories as follows:
(1) viruses, (2) bacteria, and (3) fungi and
parasites. This chapter will concern itself
with bacterial pathogens, and, in the en-
suing discussion, we will deal with the
strategies used by various bacteria to pro-
mote disease. For obvious reasons, most of
the discussions will be based on a human
serving as the host. However, it should be
noted that bacterial pathogens exist for al-
most every animal and plant life form and
that the mechanisms and strategies out-
lined for survival and causation of disease
in the human are also generally applicable
to those hosts as well. Bacterial pathogen-
esis is a large and complex topic and it
would be impossible to discuss every de-
tail in a short review such as this. Indeed,
there are myriad books that deal solely
with this topic, and the reader is directed
to these and other publications listed at
the end of this chapter for further de-
tails. Rather, this chapter is intended to
serve as a general overview to provide the
basic concepts of this complex ±eld to the
reader.
2
Concepts and Principles of Pathogenesis
A concept important to any discussion of
pathogenesis is that of virulence, which
may be de±ned as the relative ability of
an organism to cause disease. As we shall
see, the virulence of a pathogen is inti-
mately tied to a large and complex group
of factors (virulence factors, see Table 1)
that it can generate and the relative ±tness
of a given host. The ability of bacteria to
be pathogenic is directly associated with
the ability of these organisms to produce
various cell-associated or extracellular viru-
lence factors. These components are often
involved in processes such as adherence
to host cells and in the evasion of host de-
fense mechanisms. The presence of these
factors allows the bacterium to gain an ad-
vantage over the host and results in various
pathologies.
Tocaused
isease
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rgan
ismsuse
a combination of tactics, while a few
rely on a single approach. Pathogenesis
may be caused by factors produced after
the bacteria have colonized the host or
by factors that are produced exogenous
to the host. The latter case, in which
the host must contact preformed toxins
produced by the bacteria, is primarily
limited to certain forms of food poison-
ing. Interestingly, even though a large
number of pathogenic bacteria exist, re-
cent evidence demonstrates that many of
these pathogens utilize strikingly similar
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