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An AIL family protein promotes Type Three Secretion System-1 independent invasion and pathogenesis of Salmonella enterica serovar Typhi.
[typhoid]
Adhesion
and
invasion
of
intestinal
epithelial
cells
(
IECs
)
are
critical
for
the
pathogenesis
of
Salmonella
Typhi
,
the
etiological
agent
of
human
typhoid
fever
.
While
Type
Three
Secretion
System-
1
(
T
3
SS-
1
)
is
a
major
invasion
apparatus
of
Salmonella
,
independent
invasion
mechanisms
were
described
for
non-typhoidal
Salmonellae
.
Here
we
show
that
T
2942
,
an
AIL-like
protein
of
S
.
Typhi
Ty
2
strain
is
required
for
adhesion
and
invasion
of
cultured
IECs
.
That
invasion
was
T
3
SS-
1
independent
was
proved
by
ectopic
expression
of
T
2942
in
the
non-invasive
E
.
coli
BL
21
and
double
mutant
Ty
2
(
Ty
2
Δt
2942
ΔinvG
)
strains
.
Laminin
and
fibronectin
were
identified
as
the
host
binding
partners
of
T
2942
with
higher
affinity
for
laminin
.
Standalone
function
of
T
2942
was
confirmed
by
cell
adhesion
of
the
recombinant
protein
,
while
the
protein
or
anti-
T
2942
antiserum
blocked
adhesion
/
invasion
of
S
.
Typhi
,
indicating
specificity
.
A
20
amino
acids
extracellular
loop
was
required
for
invasion
,
while
several
loop
regions
of
T
2942
contributed
to
adhesion
.
Further
,
T
2942
cooperates
with
laminin-binding
T
2544
for
adhesion
and
T
3
SS-
1
for
invasion
.
Finally
,
T
2942
was
required
and
synergistically
worked
with
T
3
SS
-
1
for
pathogenesis
of
S
.
Typhi
in
mice
.
Considering
wide
distribution
of
T
2942
among
clinical
strains
,
the
protein
or
the
20
-
mer
peptide
may
be
suitable
for
vaccine
development
.
Diseases
Validation
Diseases presenting
"specificity"
symptom
familial mediterranean fever
hodgkin lymphoma, classical
inclusion body myositis
pyruvate dehydrogenase deficiency
typhoid
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