Enteroaggregative Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 249

as do previously described AggR-regulated genes ( Harrington et al., 2006 ). Col-
ony hybridization indicates that aaiA and aaiC can be found in 67% of strains
from a library of worldwide EAEC isolates ( Dudley et al., 2006 ). As expected,
the aai genes are characteristic of typical EAEC strains ( Jenkins et al., 2005 ).
The second stage ( Figure 8.2 ) of pathogenesis of EAEC involves produc-
tion of a mucus layer probably stemming from contributions of both bacteria
and intestinal mucosa. EAEC survives within the mucus layer on the surface of
enterocytes ( Hicks et al., 1996 ).
Virulence factors not regulated by AggR
The third stage ( Figure 8.2 ) of EAEC pathogenesis involves the release of tox-
ins and inducers of an inflammatory response, mucosal toxicity, and intestinal
secretion. The mechanism of EAEC-induced mucosal toxicity is not completely
elucidated ( Hicks et al., 1996 ). However, several EAEC toxins have been
described and they are encoded either on the pAA plasmid or the chromosome
( Henderson et al., 1999a , 2000 ; Henderson and Nataro, 2001 ; Okeke and Nataro,
2001 ; Boisen et al., 2009 ; Ruiz-Perez et al., 2009 ).
Infection of human intestinal explants suggests that most EAEC strains
elicit obvious mucosal damage, accompanied by rounding and exfoliation of
colonocytes. The autotransporter protease Pet is responsible for the induction
of cytotoxic effects on human intestinal explants infected with EAEC in vitro
( Henderson et al., 1999b ). However, a paradox exists: only a small minority of
EAEC strains carries the pet gene, though a much larger number of strains cause
toxic effects to explants. This paradox occurs in the context of substantial het-
erogeneity of EAEC adhesins and other putative virulence factors, presenting a
confusing clinical and epidemiologic scenario ( Huang et al., 2004b ). It has been
shown ( Huang et al., 2004b ) that most EAEC strains express, if not Pet, some
related cytotoxin, the most common of which is Sat, a cytoskeleton-cleaving
protease (like Pet), that was initially described in uropathogenic E. coli .
Serine protease autotransporters of Enterobacteriaceae (SPATEs) comprise
a large group of trypsin-like serine proteases which are secreted by Shigella
spp., uropathogenic E. coli, and all of the DEC pathotypes (see also Chapter 16)
( Benjelloun-Touimi et al., 1995 ; Stein et al., 1996 ; Brunder et al., 1997 ; Eslava
et al., 1998 ; Henderson et al., 1999a ; Al-Hasani et al., 2000 ; Guyer et al., 2000 ;
Patel et al., 2004 ). The toxins are translocated across the outer membrane by the
autotransporter pathway, in which translocation requires a dedicated C-terminal
beta barrel moiety. The N-terminal, mature SPATE toxins are 104-110 kDa in
size and feature a typical N-terminal serine protease catalytic domain, followed
by a highly conserved beta-helix motif, which is present in nearly all autotrans-
porters ( Henderson et al., 2004 ). Notably, SPATEs have not been identified in a
non-pathogenic organism ( Henderson et al., 2001 ).
The SPATEs have been organized phylogenetically into two classes. Mem-
bers of the class I SPATEs (which include Pet) are all cytotoxic to epithelial