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Interactome analyses of Salmonella pathogenicity islands reveal SicA indispensable for virulence.
[typhoid]
Serovars
of
Salmonella
enterica
,
namely
Typhi
and
Typhimurium
,
reportedly
,
are
the
bacterial
pathogens
causing
systemic
infections
like
gastroenteritis
and
typhoid
fever
.
To
elucidate
the
role
and
importance
in
such
infection
,
the
proteins
of
the
Type
III
secretion
system
of
Salmonella
pathogenicity
islands
and
two
component
signal
transduction
systems
,
have
been
mainly
focused
.
However
,
the
most
indispensable
of
these
virulent
ones
and
their
hierarchical
role
has
not
yet
been
studied
extensively
.
We
have
adopted
a
theoretical
approach
to
build
an
interactome
comprising
the
proteins
from
the
Salmonella
pathogeneicity
islands
(
SPI
)
and
two
component
signal
transduction
systems
.
This
interactome
was
then
analyzed
by
using
network
parameters
like
centrality
and
k-core
measures
.
An
initial
step
to
capture
the
fingerprint
of
the
core
network
resulted
in
a
set
of
proteins
which
are
involved
in
the
process
of
invasion
and
colonization
,
thereby
becoming
more
important
in
the
process
of
infection
.
These
proteins
pertained
to
the
Inv
,
Org
,
Prg
,
Sip
,
Spa
,
Ssa
and
Sse
operons
along
with
chaperone
protein
SicA
.
Amongst
them
,
SicA
was
figured
out
to
be
the
most
indispensable
protein
from
different
network
parametric
analyses
.
Subsequently
,
the
gene
expression
levels
of
all
these
theoretically
identified
important
proteins
were
confirmed
by
microarray
data
analysis
.
Finally
,
we
have
proposed
a
hierarchy
of
the
proteins
involved
in
the
total
infection
process
.
This
theoretical
approach
is
the
first
of
its
kind
to
figure
out
potential
virulence
determinants
encoded
by
SPI
for
therapeutic
targets
for
enteric
infection
.
A
set
of
responsible
virulent
proteins
was
identified
and
the
expression
level
of
their
genes
was
validated
by
using
independent
,
published
microarray
data
.
The
result
was
a
targeted
set
of
proteins
that
could
serve
as
sensitive
predictors
and
form
the
foundation
for
a
series
of
trials
in
the
wet-lab
setting
.
Understanding
these
regulatory
and
virulent
proteins
would
provide
insight
into
conditions
which
are
encountered
by
this
intracellular
enteric
pathogen
during
the
course
of
infection
.
This
would
further
contribute
in
identifying
novel
targets
for
antimicrobial
agents
.
Diseases
Validation
Diseases presenting
"levels of all these theoretically identified important proteins were confirmed"
symptom
typhoid
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