Mechanisms, therapeutic strategies, and emerging therapeutic alternatives for carbapenem resistance in Gram-negative bacteria
Archives of Microbiology,
Год журнала:
2025,
Номер
207(3)
Опубликована: Фев. 13, 2025
Язык: Английский
In Silico Design and Synthesis of Antifungal Peptides Guided by Quantitative Antifungal Activity
Journal of Chemical Information and Modeling,
Год журнала:
2024,
Номер
64(10), С. 4277 - 4285
Опубликована: Май 14, 2024
Antifungal
peptides
(AFPs)
are
emerging
as
promising
candidates
for
advanced
antifungal
therapies
because
of
their
broad-spectrum
efficacy
and
reduced
resistance
development.
In
silico
design
AFPs,
however,
remains
challenging,
due
to
the
lack
an
efficient
well-validated
quantitative
assessment
activity.
This
study
introduced
AFP
approach
that
leverages
innovative
metric,
named
index
(AFI),
through
a
three-step
process,
i.e.,
segmentation,
single-point
mutation,
global
multipoint
optimization.
An
exhaustive
search
100
putative
sequences
indicated
random
modifications
without
guidance
only
have
5.97–20.24%
chance
enhancing
Analysis
results
revealed
(1)
N-terminus
truncation
is
more
effective
in
activity
than
at
C-terminus
or
both
ends,
(2)
introducing
amino
acids
within
10–60%
sequence
region
enhance
aromaticity
hydrophobicity
increasing
efficacy,
(3)
incorporating
alanine,
cysteine,
phenylalanine
during
multiple
point
mutations
has
synergistic
effect
on
Subsequently,
28
designed
were
synthesized
tested
against
four
typical
fungal
strains.
The
success
rate
developing
with
minimal
inhibitory
concentration
≤5.00
μM,
was
impressive
82.14%.
predictive
tool
accessible
https://antifungipept.chemoinfolab.com.
Язык: Английский
Antimicrobial peptide Hs02 with rapid bactericidal, anti-biofilm, and anti-inflammatory activity against carbapenem-resistant Klebsiella pneumoniae and Escherichia coli
Microbiology Spectrum,
Год журнала:
2024,
Номер
13(1)
Опубликована: Дек. 3, 2024
ABSTRACT
Carbapenem-resistant
Klebsiella
pneumoniae
(CRKP)
and
Escherichia
coli
(CREC)
are
frequently
detected
in
clinical
settings,
restricting
the
use
of
carbapenems.
Therefore,
there
is
an
urgent
need
for
new
antimicrobial
strategies
to
address
infections
caused
by
CRKP
CREC.
This
study
investigated
antibacterial,
anti-biofilm,
anti-inflammatory
effects
cationic
peptide
Hs02,
along
with
its
potential
mechanisms
against
The
results
revealed
that
Hs02
had
a
low
minimum
inhibitory
concentration
(MIC)
bactericidal
(MBC)
CREC,
effectively
eliminating
bacteria
within
30
min.
Moreover,
significantly
prevents
biofilm
formation
disrupts
established
biofilms.
Further
mechanistic
studies
demonstrated
specifically
targeted
bound
bacterial
outer
membrane
lipopolysaccharides
(LPS),
disrupted
permeability
integrity,
which
led
intracellular
reactive
oxygen
species
(ROS)
accumulation.
Furthermore,
neutralized
LPS,
thereby
suppressing
production
pro-inflammatory
cytokines
TNF-α,
IL-6,
IL-1β
murine
macrophage
RAW
264.7
cells.
In
vitro
,
hemolysis
cytotoxicity
assays
confirmed
Hs02’s
safety
at
tested
concentrations
proved
improved
survival
rate
Galleria
mellonella
larvae.
conclusion,
findings
suggest
interaction
LPS
resulting
disruption
integrity
may
be
key
factors
driving
rapid
effects.
IMPORTANCE
Eukaryotic
peptides
typically
amphipathic
consisting
approximately
50
amino
acids.
Many
macromolecular
proteins
our
body
contain
polypeptide
sequences
show
characteristics
similar
those
peptides.
present
research
highlights
gap
current
literature
regarding
intragenic
derived
from
human
proteins,
exerts
demonstrate
lipopolysaccharide
(LPS)
target
activity
ability
neutralize
crucial
Язык: Английский