Type 1 and 5 secretion systems and associated toxins - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 504

Pet is required for inducing dilation of crypt openings and rounding and
extrusion of enterocytes in human tissue explants ( Henderson et al., 1999 ). The
serine-protease motif has been found to be essential for both the cytotoxicity and
enterotoxicity of Pet. Once secreted and cleaved by an autocatalytic reaction,
Pet enters eukaryotic cells, with internalization essential for cytotoxic activ-
ity. Pet is internalized by clathrin-coated vesicles and is trafficked to the Golgi
apparatus and endoplasmic reticulum. Once internalized Pet binds and cleaves
its substrate target, α-fodrin via the activity of the serine protease causing
disruption of the cytoskeleton, cell rounding and finally cell death ( Henderson
et al., 1999; Betancourt-Sanchez and Navarro-Garcia, 2009 ).
EtpA
The plasmid locus etpBAC encodes proteins that form a TPS that are required
for the glycosylation (EtpC) and secretion (EtpB) of the 170-kDa adhesin
EtpA ( Fleckenstein et al., 2006 ). EtpA was first identified as mediating adhe-
sion of the enterotoxigenic E. coli (ETEC; see Chapter 6) strain H10407 to
intestinal epithelial cells and is conserved across the ETEC pathotype ( Sahl
et al., 2011 ). EtpA is required for optimal intestinal colonization in a murine
model, suggesting it is an important virulence factor of enterotoxigenic E. coli
( Roy et al., 2008 ).
As EtpA is secreted, the protein theoretically must maintain contact with
ETEC to promote adhesion. Recent experiments discovered that EtpA mimics
and interacts with highly conserved regions of flagellin, the major subunit of
the flagellum ( Roy et al., 2009b ). The flagellin molecules capture and hold the
EtpA protein for presentation to eukaryotic receptors mediating indirect adhe-
sion between flagella and host cells ( Roy et al., 2009b ). EtpA also shares simi-
larities to proteins in other motile bacterial pathogens, suggesting a common
mode of bacterial adhesion.
UpaG
Compared to ATs, only a few TAAs have been described in E. coli. The Saa
and Eib TAA proteins range between 392 and 535 aa and have only been iden-
tified in two strains so far. In contrast, a large (~1800 aa) TAA is found in
nearly all pathogenic E. coli strains where it is known as UpaG (from UPEC)
or EhaG (from EHEC). UpaG was found to mediate adhesion to human blad-
der epithelial cells ( Valle et al., 2008b ). UpaG also promotes cell aggregation
and biofilm formation on abiotic surfaces by CFT073 and various other UPEC
strains as well as binding to the extracellular matrix (ECM) proteins fibronec-
tin and laminin ( Valle et al., 2008b ). Prevalence studies indicated that upaG
is frequently associated with extraintestinal E. coli (ExPEC) strains ( Valle
et al., 2008b ). UpaG has also been identified as a potential protective antigen in
ExPEC ( Durant et al., 2007 ).
EhaG is the positional ortholog of UpaG in EHEC O157:H7 but con-
tains significant sequence divergence within the passenger-encoding domain.