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gene, codes for a protein that belongs to the AraC family of transcriptional
activators. The C-terminal region of PerA contains a DNA-binding helix-turn-
helix motif which is highly conserved between strains (
Okeke et al., 2001
).
PerA activates the expression of
bfpA
as
perA
inactivation leads to the loss
of
bfpA
expression and thus LA (
Tobe et al., 1996
;
Okeke et al., 2001
;
Ibarra
et al., 2003
). Volunteer studies demonstrated the contribution of
perA
and
bfpA
to diarrhea, with reduced virulence displayed by mutant strains (
Bieber
et al., 1998
). PerA also auto-activates its own promoter, binding to AT-rich
regions upstream of the gene (
Martínez-Laguna et al., 1999
). This region is
significantly homologous to the PerA binding site upstream of
bfpA
(
Bustamante
et al., 1998
). PerA is closely related to VirF and Rns, the activator of the
virulence gene regulatory cascade in
Shigella flexneri
and the activator of
virulence genes in ETEC, respectively (
Dorman, 1992
). However, while VirF
and Rns could be functionally substituted (
Porter et al., 1998
;
Munson et al.,
2001
), complementation of
virF
and
rns
mutant strains was not observed with
PerA and likewise a
perA
mutant could not be complemented with either VirF
or Rns (
Porter et al., 2004
).
Apart from activating the EAF plasmid encoded genes, the
per
regulon
has been shown to activate the expression of chromosomally encoded genes
present at the LEE, including the
eae
gene (
Gómez-Duarte and Kaper, 1995
).
By ensuring adequate expression of PerC, PerA indirectly activates Ler, the
LEE transcriptional activator (see below) (
Mellies et al., 1999
;
Bustamante
et al., 2011
).
The LEE pathogenicity island and the type 3 secretion/
translocation system
The LEE is a 35.6 kb pathogenicity island. Introduction of this region into a
non-pathogenic
E. coli
strain confers the ability to induce the A/E effect (
Figure
4.1
C) (
McDaniel and Kaper, 1997
). The EPEC LEE contains 41 ORFs (
Elliott
et al., 1998
); encoding for an adhesin, the type 3 secretion system (T3SS), effec-
tor proteins, type 3 specific chaperones and transcriptional regulators. The LEE
contains five polycistronic operons, LEE1 to LEE5. The principal function of
the LEE is to form the T3SS apparatus, enabling EPEC to transport proteins
across three membranes: the cytoplasmic and outer membranes of EPEC and
the cytoplasmic membrane of the host cell to which the EPEC are attached
(
Jarvis et al., 1995
). T3SSs are composed of more than 20 proteins that form
a complex apparatus spanning both bacterial membranes and culminating in
a needle that extends from the outer membrane (see Chapter 14 for details).
The EPEC T3SS also includes the translocator proteins EspA, EspB, and EspD.
Mutations of
espA
,
espB
, or
espD
result in strains that are unable to translocate
effector proteins into host cells (
Kenny et al., 1997
;
Knutton et al., 1998
;
Taylor
et al., 1998
;
Wolff et al., 1998
;
Kenny and Jepson, 2000
) and therefore unable to
cause an A/E effect and reorganization of the host cell cytoskeleton (
Donnenberg
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