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Effective Control of Salmonella Infections by Employing Combinations of Recombinant Antimicrobial Human β-Defensins hBD-1 and hBD-2.
[typhoid]
We
successfully
produced
two
human
β-defensins
(
hBD-
1
and
hBD-
2
)
in
bacteria
as
functional
peptides
and
tested
their
antibacterial
activities
against
Salmonella
enterica
serovar
Typhi
,
Escherichia
coli
,
and
Staphylococcus
aureus
employing
both
spectroscopic
and
viable
CFU
count
methods
.
Purified
peptides
showed
approximately
50
%
inhibition
of
the
bacterial
population
when
used
individually
and
up
to
90
%
when
used
in
combination
.
The
50
%
lethal
doses
(
LD
50
)
of
hBD-
1
against
S
.
Typhi
,
E
.
coli
,
and
S
.
aureus
were
0
.
36
,
0
.
40
,
and
0
.
69
μg
/
μl
,
respectively
,
while
those
for
hBD-
2
against
the
same
bacteria
were
0
.
38
,
0
.
36
,
and
0
.
66
μg
/
μl
,
respectively
.
Moreover
,
we
observed
that
bacterium-derived
antimicrobial
peptides
were
also
effective
in
increasing
survival
time
and
decreasing
bacterial
loads
in
the
peritoneal
fluid
,
liver
,
and
spleen
of
a
mouse
intraperitoneally
infected
with
S
.
Typhi
.
The
1
:
1
hBD-
1
/
hBD-
2
combination
showed
maximum
effectiveness
in
challenging
the
Salmonella
infection
in
vitro
and
in
vivo
.
We
also
observed
less
tissue
damage
and
sepsis
formation
in
the
livers
of
infected
mice
after
treatment
with
hBD-
1
and
hBD-
2
peptides
individually
or
in
combination
.
Based
on
these
findings
,
we
conclude
that
bacterium-derived
recombinant
β-defensins
(
hBD-
1
and
hBD-
2
)
are
promising
antimicrobial
peptide
(
AMP
)
-
based
substances
for
the
development
of
new
therapeutics
against
typhoid
fever
.
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