International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(16), С. 8938 - 8938
Опубликована: Авг. 16, 2024
Previous
reports
have
demonstrated
that
the
peptide
derived
from
LfcinB,
R-1-R,
exhibits
anti-Candida
activity,
which
is
enhanced
when
combined
with
an
extract
Bidens
pilosa
plant.
However,
mechanism
of
action
remains
unexplored.
In
this
research,
a
proteomic
study
was
carried
out,
followed
by
bioinformatic
analysis
and
biological
assays
in
both
SC5314
strain
fluconazole-resistant
isolate
Candida
albicans
after
incubation
R-1-R.
The
data
revealed
treatment
R-1-R
led
to
up-regulation
most
differentially
expressed
proteins
compared
controls
strains.
These
are
primarily
involved
membrane
cell
wall
biosynthesis,
transport,
oxidative
stress
response,
mitochondrial
respiratory
chain,
DNA
damage
response.
Additionally,
C.
parental
treated
ethanolic
B.
performed.
following
were
similar
functional
processes
as
those
alone
but
mostly
down-regulated
(data
available
through
ProteomeXchange
identifier
PXD053558).
Biological
validated
results,
evidencing
surface
damage,
reactive
oxygen
species
generation,
decreased
potential.
findings
provide
insights
into
complex
antifungal
mechanisms
its
combination
extract,
potentially
informing
future
studies
on
natural
product
derivatives.
Journal of Fungi,
Год журнала:
2025,
Номер
11(5), С. 370 - 370
Опубликована: Май 12, 2025
With
rising
multidrug-resistant
yeast
pathogens,
conventional
antifungals
are
becoming
less
effective,
urging
the
need
for
adjuvants
that
enhance
their
activity
at
lower
doses.
This
study
evaluated
synergistic
of
antimicrobial
peptidomimetics
(TM8
and
RK758)
or
colistin
sulphate
in
combination
with
against
Candida
albicans,
C.
tropicalis,
parapsilosis,
Meyerozyma
guilliermondii,
Nakaseomyces
glabratus,
Pichia
kudriavzevii
Kluyveromyces
marxianus,
Candidozyma
auris
using
checkerboard
microdilution
test.
RK758
was
fluconazole
78%
isolates,
remaining
22%
isolates
still
showing
partial
synergy;
it
showed
synergy
amphotericin
B
56%
caspofungin,
exhibited
either
synergy.
TM8
44%
(with
another
44%)
67%
caspofungin
isolates.
Colistin
No
antagonism
observed
any
combinations.
Additionally,
a
time-kill
assay
further
demonstrated
between
RK758.
The
effects
these
on
cell
membrane
integrity
were
an
ergosterol
binding
assay,
supported
by
SYTOX
Green
cellular
leakage
assays,
both
indicating
lytic
effect.
These
results
suggest
can
synergise
antifungals,
offering
potential
strategy
therapy
infections.
likely
plays
role
interaction
thereby
enhancing
activities
compounds
sub-MIC
levels.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Май 20, 2025
Abstract
The
rise
of
drug-resistant
fungal
species,
such
as
Candida
auris
,
poses
a
serious
threat
to
global
health,
with
mortality
rates
exceeding
40%
and
resistance
surpassing
90%.
limited
arsenal
effective
antifungal
agents
underscores
the
urgent
need
for
novel
strategies.
Here,
we
systematically
evaluate
role
histone
H3
post-translational
modifications
in
C.
drug
resistance,
focusing
on
acetylation
mediated
by
Gcn5
Rtt109,
methylation
Set1,
Set2,
Dot1.
Mutants
deficient
these
enzymes
exhibit
varying
degrees
sensitivity.
Notably,
discover
that
GCN5
depletion
subsequent
loss
downregulates
key
genes
involved
ergosterol
biosynthesis
efflux,
resulting
increased
susceptibility
azoles
polyenes.
Additionally,
regulates
cell
wall
integrity
echinocandin
through
calcineurin
signaling
pathway
transcription
factor
Cas5.
In
infection
models
using
Galleria
mellonella
immunocompromised
mice,
deletion
significantly
reduces
virulence
.
Furthermore,
inhibitor
CPTH
2
synergizes
caspofungin
vitro
vivo
without
notable
toxicity.
These
findings
highlight
critical
pathogenicity
positioning
it
promising
therapeutic
target
combating
invasive
infections.
It
was
previously
reported
that
the
peptide
derived
from
LfcinB,
R-1-R
exhibited
anti-Candida
activity
and
this
enhanced
in
combination
with
an
extract
Bidens
pilosa
plant.
However,
mechanism
of
action
has
not
been
studied.
In
current
study,
a
proteomic
study
carried
out,
followed
by
bioinformatic
analysis
biological
assays
both
SC5314
strain
fluconazole-resistant
isolate
Candida
albicans,
after
incubation
R-1-R.
The
data
showed
treatment
two
strains,
most
differentially
expressed
proteins
comparison
to
controls
were
up-regulated.
These
mainly
involved
membrane
cell
wall
biosynthesis,
transporters,
oxidative
stress,
mitochondrial
respiratory
chain,
response
DNA
damage.
Besides,
C.
albicans
parental
treated
ethanolic
B.
also
undertaken.
similar
functional
processes
as
alone,
but
at
different
levels
mostly
down-regulated.
allowed
validation
results,
evidencing
damage
surface,
generation
reactive
oxygen
species
decrease
potential.
results
provide
information
begin
unlock
understanding
complex
antifungal
mode
peptide,
its
extract,
possibly
other
derivatives
natural
products.
Current Opinion in Infectious Diseases,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 11, 2024
Purpose
of
review
Given
the
high
mortality
and
morbidity
associated
with
invasive
fungal
diseases
(IFDs),
use
combination
antifungal
therapies
is
often
considered
despite
dearth
data.
This
aims
to
summarize
current
state
literature
therapies,
discussing
potential
roles
newer
combinations
key
considerations
for
their
clinical
use.
Recent
findings
In
infections
other
than
cryptococcal
meningitis
or
in
setting
empirical
treatment
suspected
azole-resistant
Aspergillus
infections,
utility
approaches
remains
controversial
given
paucity
well
designed
randomized
controlled
trials.
Data
on
combined
treatments
have
been
primarily
limited
in-vitro
studies,
animal
models,
case
reports
and/or
observational
studies.
With
availability
novel
agents
(e.g.
ibrexafungerp,
fosmanogepix),
therapy
treat
mould
should
be
re-visited.
A
phase
2
trial
ibrexafungerp
voriconazole
pulmonary
aspergillosis
on-going.
Summary
There
a
need
investigate
agents.
includes
delineating
indication
these
determining
how
them
most
appropriately
setting.
Frontiers in Drug Delivery,
Год журнала:
2024,
Номер
4
Опубликована: Сен. 16, 2024
Fungal
infections,
though
affecting
healthcare
globally,
receive
insufficient
attention
in
clinical
and
academic
settings.
Invasive
fungal
particularly
caused
by
combat
wounds,
have
been
identified
as
a
critical
threat
the
US
Department
of
Defense.
Monotherapy
with
traditional
antifungals
is
often
insufficient,
so
combination
therapies
are
explored
to
enhance
treatment
efficacy.
However,
systemic
treatments
can
result
severe
adverse
effects,
suggesting
need
for
localised
delivery
systems,
such
drug-loaded
electrospun
patches,
administer
directly
infection
site.
This
proof-of-concept
study
hypothesised
that
dual
amorolfine
terbinafine
therapy
slowly
releasing
from
patches
would
be
an
effective
way
eradicating
Candida
albicans
when
patch
was
applied
colony.
The
feasibility
creating
materials
loaded
antifungal
investigated.
Electrospinning
used
fabricate
polycaprolactone
(PCL)
varying
drug
loadings
(2.5%,
5%,
10%
w/w)
either
individually
or
combination.
incorporation
both
drugs
fibres
confirmed,
predominantly
amorphous
state.
Results
showed
had
significantly
greater
prolonged
effect
compared
monotherapy
larger
zones
inhibition
sustained
efficacy
over
at
least
7
days.
therefore
demonstrates
PCL-based
containing
provide
superior
activity
against
C.
patches.
approach
could
lower
required
doses,
reducing
patient
compliance
due
release,
leading
more
therapy.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 21, 2024
Abstract
The
frequent
use
of
antifungal
agents
has
contributed
to
the
emergence
previously
rare
or
unidentified
drug-resistant
fungal
species,
such
as
Candida
auris,
which
presents
mortality
rates
exceeding
40%
and
resistance
surpassing
90%.
rise
life-threatening
infections
caused
by
these
increasingly
pathogens,
coupled
with
limited
arsenal
effective
agents,
necessitates
urgent
development
novel
strategies
combat
multidrug
resistance.
In
this
study,
we
systematically
evaluated
role
post-translational
modifications
(PTMs)
histone
H3
in
drug
C.
focusing
on
acetylation
mediated
acetyltransferases
Gcn5
Rtt109,
well
methylation
methyltransferases
Set1,
Set2,
Dot1.
Mutants
deficient
enzymes
exhibited
varying
degrees
sensitivity.
Notably,
discovered
that
loss
GCN5
subsequent
downregulates
key
genes
involved
ergosterol
biosynthesis
efflux,
resulting
increased
susceptibility
major
classes
azoles
polyenes.
Additionally,
regulates
cell
wall
integrity
echinocandin
through
modulation
calcineurin
signaling
pathway
transcription
factor
Cas5.
invasive
infection
models
using
Galleria
mellonella
immunocompromised
mice,
deletion
significantly
reduced
virulence
auris.
Furthermore,
demonstrated
inhibitor
CPTH2,
when
combined
caspofungin
(CAS),
exhibits
a
synergistic
effect
against
auris
both
in
vitro
vivo
without
significant
toxicity
human
cells
mice.
conclusion,
findings
highlight
critical
pathogenicity
positioning
it
promising
therapeutic
target
for
combating
infections.
