Biology Reference
In-Depth Information
activity is produced by other A/E pathogens, including EHEC O157:H7 strains
and
C. rodentium
. The
lifA
gene is also known as Efa1 for
E
HEC
f
factor for
a
dherence as an Efa1 mutant in EHEC has significantly lower adherence to
Chinese hamster ovary cells and is deficient in human red blood cell agglutina-
tion and autoaggregation (
Nicholls et al., 2000
). A similar phenotype is seen in
EPEC, where the
efa1
mutant is considerably less adherent to epithelial cells
compared to its parent strain (
Badea et al., 2003
).
EspC
EspC is another large (110 kDa) secreted protein encoded on a pathogenicity
island of EPEC (
Vidal and Navarro-Garcia, 2008
). EspC is a member of the
SPATE (
s
erine
p
rotease
a
utotranspor
t
ers of the
e
nterobacteriaceae) family of
autotransporter proteins encoding its own transport mechanism (see Chapter
16) (
Henderson and Nataro, 2001
). Such proteins possess: (a) an N-terminal
signal sequence that promotes secretion through the inner membrane via the
sec apparatus; (b) a C-terminal domain that forms a beta barrel pore in the outer
membrane and exports; and (c) a central 'passenger' domain of the protein to
the bacterial cell surface (
Stein et al., 1996a
). Although secreted via the type
5 mechanism, EspC requires the T3SS for translocation into host cells (
Vidal
and Navarro-Garcia, 2008
). EspC causes cytotoxicity via cytoskeletal damage,
which is dependent on the internalization of the serine protease motif (
Navarro-
Garcia et al., 2004
). EspC is also an enterotoxin that induces a change in short-
circuit current in rat jejunal tissue mounted on Ussing chambers (
Mellies et al.,
2001
). The regulation of EspC is mediated by the global regulator Ler (
Mellies
et al., 1999
).
Other toxins
EAEC strains produce an enterotoxin known as enteroaggregative heat-stable
enterotoxin 1 (EAST1). A survey of diarrheagenic
E. coli
strains reported that
14 of 65 EPEC strains tested (22%) hybridized with an EAST1 probe (
Savarino
et al., 1996
). The E2348/69 strain contains two copies of the
east1
gene, one in
the chromosome and another in the EAF plasmid.
Another toxin characterized in an EPEC strain is the cytolethal distending
toxin (CDT) (
Scott and Kaper, 1994
). CDT is composed of three polypeptides
cdtA
,
cdtB
, and
cdtC
, where CDT-B is the catalytic subunit. The translocation of
CDT-B is mediated by CDT-A and CDT-C subunits. Upon reaching the nucleus,
CDT causes DNA damage (
Ohara et al., 2004
), i.e. chromatin disruption, lead-
ing to G
2
/M-phase growth arrest of the target cell and ultimately cell death
(
Lara-Tejero and Galan, 2000
). There are other sporadic reports of production
of CDT by EPEC. A study of CDT-producing
E. coli
in Bangladeshi children
found that CDT-positive EPEC strains were isolated from more children with
diarrhea than healthy controls; however, this difference did not reach statistical
significance (
Albert et al., 1995, 1996
). Another study described the possible
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