Biology Reference
In-Depth Information
Molecular pathogenesis
Mechanism of pathogenicity
Adherence to epithelial cells is probably the most important step in DAEC
infection. This process includes highly specific interaction with the epithelium
to: (i) recognize the infection site; (ii) compete and gain access to gastrointes-
tinal and urinary tract regions that are occupied by the resident microflora; and
(iii) activate signal transduction cascades that are necessary to induce diarrhea
and/or inflammation (
Benz and Schmidt, 1989
;
Bilge et al., 1989
;
Betis et al.,
2003a,b
). Many factors can contribute to DAEC adhesion to the host cells and
some adhesins have been characterized (
Betis et al., 2003a,b
). Two main adhes-
ins have been identified in DA strains, the adhesin involved in diffuse adherence
(AIDA-1) and the F1845 fimbriae (
Benz and Schmidt, 1989
;
Bilge et al., 1989
).
AIDA-1 is a plasmid-encoded 100 kDa autotransporter protein which was ini-
tially identified in an EPEC strain mediating adherence to HeLa cells and dis-
playing the DA phenotype (
Benz and Schmidt, 1989
;
Maurer et al., 1997
). The
nucleotide sequence of the F1845 fimbriae has significant homology with the
Afa/Dr family of adhesins, which are virulence determinants in uropathogenic
E. coli
strains (
Nowicki et al., 2001
). Considering that approximately 75% of
DAEC strains produce the F1845 or a related adhesin (
Bilge et al., 1989
), the
role of Afa/Dr adhesins on the DAEC pathogenesis has been the focus of several
studies.
The Afa/Dr adhesin family contains representatives of fimbrial and non-
fimbrial structures, organized in operons consisting of at least five genes and
belonging to the chaperone-usher family of adhesins. These operons are pres-
ent in both diarrheal and uropathogenic
E. coli
strains and encode for the Afa/
Dr adhesin, an invasin, and proteins required for the secretion and assembly
of the adhesin at the bacterial cell surface (see Chapter 12) (
Servin, 2005
;
Le
Bouguenec and Servin, 2006
). Afa/Dr adhesins are also classified on the basis
of the host cell receptors that they bind, such as the Dr(a) blood-group antigen
present on the decay-accelerating factor (DAF, CD55), the extracellular matrix
protein collagen IV and/or carcinoembryonic antigen-related cellular adhesion
molecules (CEACAMs) (
Nowicki et al., 2001
;
Berger et al., 2004
). All these
receptors play a pivotal role in DEAC adherence to the gastrointestinal and uri-
nary tract.
Adherence
Using polarized epithelial cultured cells it was established that Afa/Dr adhes-
ins interact with DAF or CEACAM receptors (CEACAM6 for F1845) and,
as a result, the receptors accumulate underneath the bacteria (
Goluszko
et al., 1999
;
Le Bouguenec et al., 2001
). This interaction also triggers sig-
nal transduction cascades that control the growth of long finger-like cellular
projections (lamellipodia) which wrap around the bacteria, promoting tight
attachment of the bacteria to the cell surface (
Cookson and Nataro, 1996
).
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