Enterotoxigenic Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 185

ETEC virulence. Despite some early enthusiasm for targeting type 1 pili in
combination ETEC vaccines ( Levine, 1981 ), initial efforts to protect against
ETEC infections by vaccination with type 1 pili were disappointing ( Levine
et al., 1982 ). Nevertheless, tremendous advances in our understanding of the
biogenesis of type 1 pili ( Waksman and Hultgren, 2009 ), the very complex
nature of their role in UPEC infections ( Mulvey et al., 2000 ; Schilling et al.,
2001 ), and recognized diversity in FimH tip adhesin ( Sokurenko et al., 1997 )
structures could stimulate additional examination of a role for these highly
conserved fimbriae in ETEC pathogenesis and vaccine development.
E. coli common pili (ECP)
The genomes of most E. coli encode a variety of potential pilus systems.
E. coli common pili (ECP), originally discovered in enterohemorrhagic
E. coli ( Rendon et al., 2007 ) and commensal organisms, are also expressed by
other E. coli pathotypes, including ETEC ( Blackburn et al., 2009 ). Although
at present, the contribution of these structures to the pathogenesis of ETEC is
uncertain, they could act in concert with other adhesins as has been noted for
EPEC ( Saldana et al., 2009 ).
Outer membrane proteins
Two outer membrane proteins that have been identified in some strains of ETEC
promote invasion of intestinal epithelial cell lines in vitro. These include Tia,
a 25 kDa ( Fleckenstein et al., 1996, 2002 ) heparin sulfate binding outer mem-
brane protein encoded on a pathogenicity island of ETEC H10407 ( Fleckenstein
et al., 2000 ), and TibA ( Elsinghorst and Weitz, 1994 ), a glycosylated autotrans-
porter protein ( Lindenthal and Elsinghorst, 1999 ). Glycosylation of TibA likely
requires TibC, a hepatosyltransferase ( Moormann et al., 2002 ). The relevance
of epithelial cell invasion per se in the pathogenesis of ETEC remains uncertain,
but it is likely that the in vitro invasion phenotype reflects intimate interactions
between the bacteria and the host.
Novel antigens
A modified Tn phoA mutagenesis strategy to identify secreted or surface-
expressed antigens from ETEC led to the identification of a two-partner secretion
locus ( Fleckenstein et al., 2006 ) encoded on the large 94.8 kb virulence plasmid
of ETEC H10407 that also encodes CFA/I (see Figure 6.2 b). Three contiguous
genes, etpB , etpA, and etpC encode an outer membrane transport pore (EtpB),
a secreted glycoprotein adhesin (EtpA), and a putative transglycosylase (EtpC).
Interestingly, EtpA appears to promote ETEC adhesion in a unique fashion by
bridging highly conserved flagellin residues exposed only at the tips of ETEC
flagella, with receptors on the mucosal surface ( Roy et al., 2009 ).
A similar strategy was also used to identify EatA ( Patel et al., 2004 ), a
secreted serine protease autotransporter (SPATE) molecule, which is also