Biology Reference
In-Depth Information
Ler (LEE-encoded regulator)
Ler is a 15-kDa protein encoded by the first gene in the LEE1 operon (
Mel-
lies et al., 1999
). Ler regulates the expression of LEE as well as some non-
LEE-encoded genes (
Elliott et al., 2000
). This protein induces expression by
counteracting the repression mediated by nucleoid-associated protein H-NS
(
Bustamante et al., 2001
). H-NS binds to AT-rich sequences and negatively
modulates expression of a number of genes (
Atlung and Ingmer, 1997
).
Expression of Ler is influenced by many factors in response to environmen-
tal signals (
Mellies et al., 2007
) including quorum sensing (
Sperandio et al.,
1999
). Quorum sensing activates quorum-sensing
E. coli
regulator A (QseA),
which activates transcription of Ler independent of
per
(
Sircili et al., 2004
).
Ler expression is also dependent on integration host factor (IHF). IHF posi-
tively regulates
ler
by binding upstream of the
ler
promoter (
Friedberg et al.,
1999
). GlrA (Global Regulator of LEE-Activator) and GrlR (Repressor)
encoded within the LEE positively and negatively regulate Ler expression
respectively (
Deng et al., 2004
). PerC, encoded in the EAF plasmid, has also
been shown to induce the expression of Ler (
Lio and Syu, 2004
), indepen-
dent of activation via GlrA (
Bustamante et al., 2011
). Ler is also a negative
auto-regulator (
Berdichevsky et al., 2005
). It binds to the LEE1 regulatory
region to reduce Ler, enabling the activation of the LEE2, LEE3, and other
promoters.
Other virulence factors
Lymphostatin/Efa1
The
lifA
gene, encoding a 366-kDa protein lymphostatin, is located on the IE6
pathogenicity island. This pathogenicity island also encodes several non-LEE-
encoded effectors (
Iguchi et al., 2009
). To date, lymphostatin is the largest T3S
effector protein identified (
Deng et al., 2012
), both in EPEC and EHEC. The
prevalence of this locus in EHEC strains isolated from patients with hemolytic
uremia and outbreak strains suggests it may play a role in virulence (
Afset et al.,
2006
;
Wickham et al., 2006
). A portion of lymphostatin displays sequence simi-
larity to the glycosyltransferase region of large clostridial cytotoxins, which is
required for glycosylation of the Rho family GTPases (
Klapproth et al., 2000
).
A
lifA
mutant of
Citrobacter rodentium
was deficient in decreasing epithelial
barrier function. This change was dependent on the glycosyltransferase region
and was associated with a decreased activation of GTPase Cdc42 (
Babbin et al.,
2009
). Multiple functions have been described for this extremely large protein.
C. rodentium
lymphostatin is also involved in bacterial colonization, crypt
cell proliferation, and epithelial cell regeneration (
Klapproth et al., 2005
). In
EPEC, lymphostatin inhibits the transcription of many lymphokines, including
interleukin 2, interleukin 4, and interferon-γ, and inhibits lymphocyte prolifera-
tion (
Klapproth et al., 1995, 1996, 2000
;
Malstrom and James, 1998
). Similar
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