Enteroaggregative Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 250

cells ( Dutta et al., 2002 ). In addition to Pet, the class I SPATEs include among
others EspP from enterohemorrhagic E. coli , EspC from enteropathogenic
E. coli , SigA from Shigella flexneri , and Sat, from uropathogenic and diffusely
adhering E. coli ( Henderson and Nataro, 2001 ). Class II SPATEs are more
diverse with regard to phenotype, though several are known to cleave mucin.
This class comprises, among others, Pic and SepA from EAEC and S. flexneri
( Benjelloun-Touimi et al., 1995 ; Henderson et al., 1999a , Harrington et al.,
2009) and Tsh from avian pathogenic E. coli ( Provence and Curtis 1994 ). Class
II separates further into two subclasses where one comprises of several potential
O-glycoproteases (Ruiz-Perez et al., unpublished).
Pet is a protease encoded on the pAA plasmid of strain 042 and other EAEC
strains ( Eslava et al., 1998 ). The prevalence of Pet among EAEC isolates var-
ies between 18-44%, although the toxin is unique to EAEC ( Vila et al., 2000 ;
Yamazaki et al., 2000 ). The toxin enters the eukaryotic cell and moves through
the vesicular system which appears to be required for the induction of cyto-
pathic effects ( Navarro-Garcia et al., 2001 ). It has been shown that Pet cleaves
erythroid spectrin in vitro and Pet intoxication is accompanied by degradation
of spectrin species (components of the cytoskeleton) and clumping of spectrin
in intoxicated HEp2 cells ( Villaseca et al., 2000 ; Sui et al., 2003 ). The muco-
sal intestinal toxicity of Pet results in dilation of crypt openings ( Figure 8.4 ),
rounding and exfoliation of colonic enterocytes, widening of intercrypt crevices
and loss of apical mucus from goblet cells ( Henderson and Nataro, 1999 ).
Sat is cytotoxic to urinary epithelial cells in vitro ( Guyer et al., 2000 ), and
Sat induces cytoskeletal perturbation in intestinal epithelium accompanied by
rearrangement of tight junction proteins ( Guignot et al., 2007 ). Though the fun-
damental mode of action of Sat is unknown, it was suggested that the protein
enters epithelial cells and directly cleaves spectrin ( Maroncle et al., 2006 ), an
effect also seen in Pet ( Canizalez-Roman et al., 2003 ).
The sigA gene is situated on the she pathogenicity island of Shigella flexneri
2a which also contains the pic gene. SigA is a IgA protease-like homolog lying
3.6 kb downstream and in a reverted orientation with respect to pic ( Rajakumar
et al., 1997 ). Mature SigA is 103 kDa, slightly smaller than the other class 1
SPATE proteins ( Al-Hasani et al., 2000 ). Al-Hasani et al. (2000) showed that
SigA is secreted as a temperature-regulated serine protease capable of degrad-
ing casein; these investigators also reported that SigA is cytopathic for HEp-2
cells, suggesting that it may be a cell-altering toxin with a role in the pathogen-
esis of Shigella infections. SigA was at least partly responsible for the ability of
S. flexneri to stimulate fluid accumulation in ligated rabbit ileal loops.
Two EAEC toxins are encoded on the same chromosomal locus, embedded
on opposite strands. The larger gene encodes Pic. The opposite strand encodes
the oligomeric enterotoxin that is known as Shigella enterotoxin 1 (ShET1,
encoded by setAB genes), owing to its presence in most Shigella flexneri of
serotype 2a ( Fasano et al., 1997 ; Henderson et al., 1999b ). Hence ShET1 is
encoded within the pic open-reading frame, on the antisense strand. It is thought