Biology Reference
In-Depth Information
Shigella
, is
ompT
, a prophage-mediated gene encoding a surface protease. This
protease degrades IcsA/VirG, a virulence protein in
Shigella
that is required
for keratoconjunctivitis in guinea pigs and is involved in intra- and intercel-
lular motility (
Nakata et al., 1993
). The gene
ompT
is lacking in all lineages of
Shigella
, also fulfilling the criteria to be an antivirulence gene. Multiple inde-
pendent evolutionary origins of
Shigella
strains indicate convergent evolution
via the loss of antivirulence factors, including inactivation/deletion of LDC by
different mechanisms, which is a strong indication for the action of positive
selection (
Pupo et al., 2000
).
Even a clean single gene deletion, however, could potentially result in toxic
effects by disrupting, for example, biogenesis pathways and build-up of interme-
diate components (
Holt et al., 2008
). That is possibly why multiple gene or entire
gene operons/clusters tend to be lost, resulting in so-called 'black holes' in the
genomes (
Maurelli, et al., 1998
). Instead of gene deletion, 'loss of function' can
also be achieved by a mutation introducing premature stop codons or by frame-
shift mutations that disrupt the reading frame. However, such mechanisms result
in expression of truncated and/or misfolded proteins that could be toxic for the
bacterial cell (
Kuo and Ochman, 2010
). In contrast, loss-of-function due to muta-
tion in the active site of the protein might provide a better way to achieve the adap-
tive effect. Mutations in the active protein site have been reported, for example,
in the major, type 1 fimbrial adhesin of
E. coli
species, FimH, where inactivating
mutations are found in the mannose-binding pocket of the adhesive protein of
some EHEC isolates (
Shaikh et al., 2007
). Loss of the type 1 fimbrial function has
been also seen for
Shigella
and is likely to provide some kind of pathogenicity-
adaptive effect in enteric pathogens (
Snellings et al., 1997
).
Gene variation
Point mutations that do not inactivate but modify the function of coded protein
are another important player of the pathoadaptive mechanism of
E. coli
evo-
lution. An example of pathoadaptive point mutation is the evolution of
fimH
gene encoding the type 1 fimbrial adhesin in
E. coli
(see Chapter 12). FimH
is expressed by >90% of
E. coli
(
Johnson and Stell, 2000
), and uropathogenic
isolates express some specific variants of FimH owing to accumulation of point
mutations (
Weissman et al., 2006
). These variants significantly enhance binding
to mannosylated glycoproteins on uroepithelial cell surfaces, thereby increas-
ing bacterial tropism to uroepithelium (
Sokurenko et al., 1998
;
Hommais et al.,
2003
). Point mutations leading to functional modification that is pathoadaptive
in nature have been shown in at least two other types of
E. coli
adhesins - Dr
family (
Korotkova et al., 2007
) and class 5 fimbrial adhesins in enterotoxigenic
isolates (
Tchesnokova et al., 2010
;
Chattopadhyay et al., 2012
).
Non-coding mutations
Nucleotide point mutations may also have adaptive effects by affecting the rate
of gene transcription or translation. Such mutations could be comparable to the
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