Bacterial Pathogenesis, Molecular Basis of
In the genetic sense, a bacterium can
become pathogenic by one of a number of
events. The organism could harbor genes
unique to itself. A good example of such
genes is the ‘‘pathogenicity islands’’ (PAIs)
that have been identiFed in numerous
species of bacterial pathogens. PAIs are
encode genes required for the expression
and production of virulence factors and
that are absent from nonpathogenic related
bacteria. The PAIs can range in size from
10 to 200 kb and thus can encode few or
many genes important for virulence. Many
of the identiFed PAIs are located between
loci that encode transfer RNA, sites that are
frequently used by speciFc bacteriophages
as integration sites. This Fnding suggests
that the acquisition of a PAI by a given
organism can be accomplished simply
by the infection of the bacterium with
a phage harboring the DNA as part of
its genome. This horizontal gene transfer
concept is further supported by the Fnding
that PAIs are usually flanked by direct
repeat sequences that indicate that the
region is prone to recombination events
such as those necessary for the integration
of a foreign fragment of DNA. ±urther
evidence for the concept that the PAI
is acquired from a different organism is
that they often exhibit G
are signiFcantly different from that of the
organism in which they are found. Implicit
in this Fnding is that transfer of a PAI
between organisms could be accomplished
simply by infection with a bacteriophage
that is able to infect both organisms.
It should be noted that PAIs are not
the only virulence elements that can be
acquired by horizontal transfer. ±or ex-
ample, many of the genes required for
the virulence of
Shigella spp
tained on a large plasmid carried by the
pathogenic strain.
is also able to
produce a number of cytotoxins, the genes
for which are carried by a bacteriophage
that has integrated into the chromosome.
This bacteriophage has also been shown to
be transferred to the enterohemorrhagic
strains of
Escherichia coli
able to produce the cytotoxins. Thus, the
transfer of genes encoding virulence fac-
tors within the same specie or between
species has been documented and pro-
vides a mechanism for the acquisition of
virulence capabilities by organisms that
were previously avirulent.
A second mechanism by which a bac-
terium can evolve to pathogen status is via
the loss of a function required for sup-
pression of virulence factor expression.
Suppressors, as the name implies, func-
tion to maintain the expression of a given
gene(s) quiescent. One of the Frst exam-
ples of such a mechanism was the loss
of the OmpT surface protease of
This protease suppresses virulence since
its expression interferes with the expres-
sion of the VirG protein, which is required
for intercellular spread. The regions of
DNA corresponding to the genes that have
been lost are known as
black holes
to con-
trast them with the PAIs whose acquisition
leads to increased virulence.
A bacterial species may become more
virulent by the differential regulation of
pression of the same functional group of
genes may be regulated by different envi-
ronmental controls. An excellent example
of such differential regulation occurs again
in the genus
S. enterica
harbor very similar genes encoding
functions required for cellular invasion.
However, the
S. enterica
genes respond to
oxygen tension, while the expression of the
S. flexneri
cohort of genes is modulated by
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