Biology Reference
In-Depth Information
Pathoadaptive mutations
Pathoadaptive mutation is an alternative mechanism for the virulence evolution
that involves genetic alteration of the existing genome components rather than
acquisition of novel genes. The major mechanisms are gene amplification, inac-
tivation, and variation (
Figure 3.2
).
Gene amplification
Amplification of gene copies can lead to increased production of the corre-
sponding protein and, if that confers an advantage for the pathogen, be selected
during the infection. It has been proposed recently that transient amplification
of genetic regions is a common phenomenon in
E. coli
(and other bacteria),
allowing for fast adaptation in environments and increased rates of adaptive
evolution (
Kugelberg et al., 2006
). Thus, gene amplification might be a more
significant phenomenon than appreciated previously. Examples of virulence
factors with multiple copies are Acriflavin resistance protein D (AcrD) in EPEC
(
Fukiya et al., 2004
); Iha adhesin in EHEC (
Mellmann et al., 2009
); P-fimbrial
genes in some UPEC (
Kao et al., 1997
).
Gene duplication is another critical event commonly found in many enteric
pathogens including
E. coli
(
Ohno, 1970
;
Himmelreich et al., 1996
;
Tomb et al.,
1997
), providing means for novel functional evolution. An important example
is the duplication of Shiga toxin 2 encoding genes (
stx
2
) found in some EHEC
O157:H7 outbreak strains (
Muniesa et al., 2003
), and in vitro experiments
showed correlation of the occurrence of duplicated genes with increased pro-
duction of Stx2 (
Bielaszewska et al., 2006
). Studies showed that evolution of
orthologs faces considerable selective constraints (
Hughes and Hughes, 1993
),
and the level of functional constraints reduces immediately following a duplica-
tion event resulting in a significantly higher rate of evolution between paralogs
(
Lynch and Conery, 2000
;
Jordan et al., 2002
;
Kondrashov et al., 2002
).Thus,
duplication allows the emergence of proteins with novel structure and func-
tions. For example, the
cspA
(the major cold-shock protein) family homologs in
E. coli
resulted from a number of gene duplication events allowing emergence
of specific groups of genes that adaptively respond to different environmental
stresses such as cold-shock stress (
cspA
,
cspB
,
cspG
), nutritional deprivation
(
cspD
), etc. (
Yamanaka et al., 1998
).
Gene inactivation (anti-virulence factors)
HGT and gene amplification are so-called the 'gain-of-function' mechanisms
for the evolution of microbial virulence. Another and quite common mechanism
represents 'loss-of-function' that includes gene or coded protein inactivation
via point substitution, frameshift mutation, insertion sequence acquisition, and
gene deletion. This mechanism is often crucial to enhance the fitness of a patho-
gen in a novel environment.
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