Biology Reference
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gain- or loss-of-function mutation of the coding genes themselves. For example,
increased/decreased gene expression could also be achieved by mutations in the
non-coding regulatory regions (e.g. promoters, operators, etc.), while protein
expression could be affected by mutation in ribosome-binding sites (
Corvec
et al., 2007
;
Mammeri et al., 2008
;
Smet et al., 2008
). Another type of mutation,
the importance of which has been recently recognized, is silent (synonymous)
mutations in the coding genes (
Kudla et al., 2009
). These mutations do not
affect the protein structure but can have a significant effect on the gene transla-
tion rate by introducing or eliminating rare codons or by modifying the tertiary
structure (and, thus, for example stability) of the messenger RNA. Therefore,
the silent mutations might not be that 'silent'!
EVOLUTIONARILY ADAPTED AND PRE-ADAPTED VIRULENCE
FACTORS
While we understand relatively well the genetic mechanisms of virulence evo-
lution, the exact nature of the virulence factors is not fully understood. Some
of the examples of virulence factors that are critical for the ability of
E. coli
to
cause specific types of infections are mentioned here. Others are discussed in
more detail in various chapters of this topic. However, in defining whether or
not specific genes and/or phenotypic traits are virulence factors, we primarily
rely on two rather imperfect approaches: (a) experimental, i.e. animal or cell
models of the infection; and (b) epidemiological, i.e. genes/traits more com-
mon among pathogens. The experimental models are very important and led
us to many major discoveries, but they could also be misleading. The patho-
gen's ability to survive and cause damage within a host compartment is often
finely tuned to very specific conditions there that could be difficult to reproduce
under the model conditions. The epidemiological analysis also does not provide
a straightforward answer on the exact nature of the virulence factors. While by
definition the genome of a given clinical isolate encodes all virulence factors
necessary for the infection to take place, the main issue is to understand which
of the genes/traits are directly relevant to the isolate's ability to cause the infec-
tion. As mentioned above, comparing content of multiple isolates from patients
and healthy individuals (or environment) helps to narrow down the important
genes. However, many if not most of the genes or traits associated specifically
with pathogenic
E. coli
isolates might not be relevant to the pathogenicity per
se. Furthermore, this approach ignores important host factors that influence the
outcome of infection.
Even for well-defined, proven virulence traits, uncertainty could remain
whether such traits have evolved to serve during the infection or only acciden-
tally fit to do so. This brings us to a key question about virulence factors
from evolutionary perspectives - did they evolve or not to function during the
infection in humans? Any phenotypic trait could be defined as an evolutionarily
adapted or pre-adapted trait (
Van Derlinden et al., 2008
). The adapted trait is the
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