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We have described in EAEC several putative pathogenicity islands that may
encode additional virulence factors, as predicted from in silico homology to
better characterized systems. Some EAEC strains encode a type 3 secretion
system called ETT-2; putative effectors for this system were found elsewhere on
the genome (
Sheikh et al., 2006
). Moreover, we have shown that these putative
effectors are under transcriptional control of a factor called EilA, homologous
to the HilA activator from
Salmonella
strains. EilA also activates the bacterial
surface protein Air, which features predicted immunoglobulin-like repeats. This
new putative virulence-related regulon in EAEC may include adherence and
aggregation (
Sheikh et al., 2006
).
INFLAMMATION IN EAEC PATHOGENESIS
EAEC is an inflammatory pathogen, as demonstrated both in clinical (
Green-
berg et al., 2002
) and laboratory (
Steiner et al., 1998
) reports. Clinical stud-
ies have shown that lactoferrin, IL-8, and IL-β can be detected in feces from
cases of EAEC diarrhea at a higher level than in stools of patients infected with
non-EAEC diarrhea (
Jiang et al., 2002
). The virulence factors of typical EAEC
(including
aggA
,
aggR
,
aafA
, and
aap
) are associated with increased levels of
fecal cytokines and inflammatory markers, and may be observed whether or not
the patient manifests diarrhea. The inflammatory effect was linked to expres-
sion of a novel EAEC flagellin protein (
Donnelly and Steiner, 2002
), which
is homologous to a flagellin encoded by
S. dysenteriae
. The EAEC flagellin
induced IL-8 from intestinal epithelial cells (IECs) in culture (
Steiner et al.,
1997
,
1998
).
It was shown that flagellin was the major pro-inflammatory factor of EAEC
on intestinal epithelial cells in culture (
Okhuysen and Dupont, 2010
). Infec-
tion of polarized monolayers of the human colonic intestinal cell line T84 with
EAEC strain 042 caused both IL-8 release (
Harrington et al., 2005
) and a drop
in trans-epithelial electric resistance (TEER) when compared with the unin-
fected control and with non-pathogenic
E. coli
HS (
Strauman et al., 2010
). It
is now confirmed in vitro that the fimbriae mediate release of IL-8 and drop in
TEER. Furthermore it was shown that AAF/II fimbriae are sufficient to induce
transmigration of neutrophils across an epithelial layer in vitro (
Qadri et al.,
1994
). Since a suitable animal model is not in use, a xenotransplant model was
used and it was shown that the aggregative fimbriae are important in the devel-
opment of inflammation in the human intestine. These data suggest that the
AAF adhesins may be not only colonization factors, but may also be both nec-
essary and sufficient for induction of mucosal inflammation (
Boll et al., 2012
).
STRAIN HETEROGENEITY
EAEC strains belong to a diverse range and combination of O:H serotypes
(
Vial et al., 1988
;
Yamamoto et al., 1992
;
Qadri et al., 1994
;
Huppertz et al.,
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