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gene in strain 042 increased fitness for growth in mucus scraped from the
surface of the mouse intestine. Moreover,
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mutants in EAEC are less adept
at colonizing the mouse intestine, whereas a
Shigella pic
mutant elicited less
intense intestinal inflammation in the rabbit ligated-loop model (
Henderson and
Nataro, 2001
).
The ShET1 (55-kDa) mode of action has not been defined, but it does not
appear to act via the traditional mechanisms of toxin-induced intestinal secre-
tion, such as via cyclic AMP and cyclic GMP. ShET1 induces fluid secretion
in mucosal tissue explants but does not induce cytotoxic effects (
Fasano et al.,
1997
). Studies have suggested that most EAEC strains from patients with diar-
rhea express the ShET1 toxin (
Czeczulin et al., 1999
;
Vila et al., 2000
). ShET1
may contribute to the secretory diarrhea that accompanies EAEC and
Shigella
infections (
Kaper et al., 2004
).
SepA, a SPATE toxin, was originally described in
Shigella flexneri
2a,
where it is among the most abundant secreted proteins. The protease is encoded
on the
Shigella
virulence plasmid, suggesting a contribution to pathogenicity
(
Benjelloun-Touimi et al., 1995
). Using human colonic tissue, it was shown that
purified SepA toxin elicits mucosal damage (
Coron et al., 2009
). SepA mutants
of
S. flexneri
induced less mucosal inflammation in ligated rabbit ileal loops
compared with the wild-type parent strain (
Benjelloun-Touimi et al., 1998
). The
precise mode of action of SepA remains to be discovered. We have found SepA
to be common and epidemiologically important among EAEC strains: among
EAEC strains isolated from a case-control study of children's diarrhea in Mali,
SepA was the only factor strongly associated with diarrheal illness (
Boisen
et al., 2012
).
The first EAEC virulence factor that was implicated as a potential cause of
diarrhea was the enteroaggregative heat-stable toxin, EAST1. Epidemiological
studies demonstrate that EAST1 is not only associated with EAEC but is also
present in a wide range of pathogenic
E. coli
such as ETEC, DAEC, entero-
pathogenic
E. coli
(EPEC), and enterohemorrhagic
E. coli
. Furthermore,
E. coli
strains harboring no known virulence factors other than EAST1 were found in
the feces of humans with diarrhea (
Paiva de Sousa and Dubreuil, 2001
;
Menard
and Dubreuil, 2002
). EAST1 is encoded by the
astA
gene which spans 117 bp.
It is a 38-aminoacid peptide with homology to the heat-stable (ST) enterotoxin
of ETEC (
Savarino et al., 1991
,
1993
). The
astA
gene can be found on either
plasmids or on the chromosome, and sometimes both, in one or several copies
(
Menard and Dubreuil, 2002
). EAST1 is immunologically different from STa,
as no cross-neutralization was observed with polyclonal anti-STa antibodies
(
Savarino et al., 1996
). It is conceivable that EAST1 could contribute to watery
diarrhea in EAST1-positive EAEC strains (41% of EAEC strains harbor the
astA
gene). However, the
astA
gene is also present in up to 38% of commensal
E. coli
strains (
Savarino et al., 1996
;
Yamamoto and Echeverria, 1996
;
Zhou
et al., 2002
). EAST1 may exist as a series of allelic variants, some of which may
be more virulent than others (
Menard et al., 2004
).
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