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et al., 1990a,b
,
1993a,b,c
;
Foubister et al., 1994a,b
;
Kenny et al., 1996
;
Abe
et al., 1997, 1998
;
Kenny and Finlay, 1997
;
Lai et al., 1997
;
Nougayrède et al.,
1999
). EspB is required for virulence in volunteers (
Tacket et al., 2000
), while
in a rabbit model, EspA, EspB, and EspD have each been shown to be required
for virulence (
Abe et al., 1998
). EspA is a component of a prominent filamen-
tous structure that connects EPEC to host cells (
Knutton et al., 1998
). It forms
a sheath around the needle complex which is encoded by
escF
(
Sekiya et al.,
2001
;
Wilson et al., 2001
). EspB and EspD are both localized to the host cell
membrane after attachment and together, these proteins form the translocation
pore (
Knutton et al., 1998
;
Wolff et al., 1998
;
Wachter et al., 1999
;
Ide et al.,
2001
;
Luo and Donnenberg, 2011
). In addition, EspB has been shown to be
an effector protein secreted by the T3SS. EspB binding to α-catenin (
Kodama
et al., 2002
) and myosin (
Iizumi et al., 2007
) within the host cell regulates actin
cytoskeletal rearrangement and thus promotes morphological changes (
Taylor
et al., 1999
).
Recently, other proteins have been identified as being crucial for the T3SS.
EscA, a small protein encoded by Orf15, localizes to the periplasm, associates
with the inner membrane, interacts with outer membrane secretin EscC and is
required for the structural integrity of the T3SS complex (
Sal-Man et al., 2012a
).
EscI has also been shown to be essential for T3S and may function as an inner
rod protein and act as an early secreted effector (
Sal-Man et al., 2012b
). EscI
interacts with EscU, which is an essential inner membrane ring of the T3SS
that self-cleaves to form a secretin-competent state for accommodating effec-
tors (
Zarivach et al., 2008
;
Thomassin et al., 2011
). The EscF needle protein
associates with multiple proteins: EscD, an inner membrane structural protein,
EscJ, an inner ring protein, and EscC. EscC, EscD, and EscJ are required for
the formation of the T3SS apparatus (
Ogino et al., 2006
). EscI, EscU, EscF, and
the chaperone CesT also interact with EscP (Orf16) (
Monjaras et al., 2012
).
While EscP is not an essential protein of the T3SS, it appears to be required
for regulating needle length and participating in substrate specificity (
Monjaras
et al., 2012
). EscN is a type III ATPase (
Andrade et al., 2007
) that provides a
potential energy source for the unfolding of T3S effectors (
Song et al., 2004
;
Zarivach et al., 2007
).
Delivery of effectors by the T3SS leads to the interaction between the
products of two highly characterized genes in the LEE,
eae
and
tir
, encoding
intimin and Tir, respectively. Intimin is a 94-kDa outer membrane adhesin
(
Jerse and Kaper, 1991
) required for the intimate attachment of EPEC to epi-
thelial cells at the site of A/E lesions (
Figure 4.1
C) (
Jerse et al., 1990
), while
Tir is the
t
ranslocated
i
ntimin
r
eceptor which binds intimin at the host cell
surface (
Kenny et al., 1997
). While intimin is not strictly required for EPEC
protein secretion or translocation (
Rosenshine et al., 1992
;
Foubister et al.,
1994b
;
Haigh et al., 1995
;
Kenny and Finlay, 1995, 1997
;
Wolff et al., 1998
),
the absence of intimin results in a significant decrease in EspB translocation
(
Wolff et al., 1998
) and intiminis required for full virulence in human and
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