Two-component
signal
transduction
systems
(TCSs)
are
regulatory
widely
distributed
in
eubacteria,
archaea,
and
a
few
eukaryotic
organisms,
but
not
mammalian
cells.
A
typical
TCS
consists
of
histidine
kinase
response
regulator
protein.
Functional
mechanistic
studies
on
different
TCSs
have
greatly
advanced
the
understanding
cellular
phosphotransfer
mechanisms.
In
this
concept
paper,
we
focus
His-Asp
mechanism,
ATP
synthesis
function,
antimicrobial
drug
design,
biosensors
protein
allostery
mechanisms
based
recent
investigations
to
inspire
new
applications
future
research
perspectives.
Journal of Leukocyte Biology,
Год журнала:
2024,
Номер
116(3), С. 469 - 486
Опубликована: Март 18, 2024
Abstract
Fungal
infections
present
a
significant
global
public
health
concern,
impacting
over
1
billion
individuals
worldwide
and
resulting
in
more
than
3
million
deaths
annually.
Despite
considerable
progress
recent
years,
the
management
of
fungal
remains
challenging.
The
limited
development
novel
diagnostic
therapeutic
approaches
is
largely
attributed
to
our
incomplete
understanding
pathogenetic
mechanisms
involved
these
diseases.
Recent
research
has
highlighted
pivotal
role
cellular
metabolism
regulating
interaction
between
fungi
their
hosts.
In
response
infection,
immune
cells
undergo
complex
metabolic
adjustments
meet
energy
demands
necessary
for
an
effective
response.
A
comprehensive
circuits
governing
antifungal
immunity,
combined
with
integration
individual
host
traits,
holds
potential
inform
medical
interventions
infections.
This
review
explores
insights
into
immunometabolic
regulation
host–fungal
interactions
infection
outcome
discusses
how
repurposing
cell
function
could
be
exploited
innovative
personalized
approaches.
Biochimica et Biophysica Acta (BBA) - Bioenergetics,
Год журнала:
2024,
Номер
1865(2), С. 149031 - 149031
Опубликована: Янв. 7, 2024
Fungal
pathogens
present
a
growing
threat
to
both
humans
and
global
health
security
alike.
Increasing
evidence
of
antifungal
resistance
in
fungal
populations
that
infect
plant
species
has
increased
reliance
on
combination
therapies
shown
the
need
for
new
therapeutic
targets
be
investigated.
Here,
we
review
roles
mitochondria
respiration
pathogenesis
discuss
role
Alternative
Oxidase
enzyme
(Aox)
human
phytopathogens.
exists
Aox
within
mechanisms
underpin
virulence.
also
plays
important
adaptability
may
prove
useful
dual
targeted
fungal-specific
approaches.
As
improved
specific
mitochondrial
inhibitors
are
under
development
see
this
as
an
emerging
target
future
approaches
tackling
challenge
infection.
Marine Drugs,
Год журнала:
2024,
Номер
22(1), С. 38 - 38
Опубликована: Янв. 8, 2024
Mangrove-derived
actinomycetes
represent
a
rich
source
of
novel
bioactive
natural
products
in
drug
discovery.
In
this
study,
four
new
polyene
macrolide
antibiotics
antifungalmycin
B-E
(
Journal of Molecular Biology,
Год журнала:
2024,
Номер
436(8), С. 168513 - 168513
Опубликована: Март 5, 2024
Systemic
fungal
infections
are
a
growing
public
health
threat,
and
yet
viable
antifungal
drug
targets
limited
as
fungi
share
similar
proteome
with
humans.
However,
features
of
RNA
metabolism
the
noncoding
transcriptomes
in
distinctive.
For
example,
harbor
highly
structured
elements
that
humans
lack,
such
self-splicing
introns
within
key
housekeeping
genes
mitochondria.
location
function
these
mitochondrial
riboregulatory
has
largely
eluded
characterization.
Here
we
used
an
RNA-structure-based
bioinformatics
pipeline
to
identify
group
I
interrupting
medically
relevant
fungi,
revealing
their
fixation
handful
genetic
hotspots
ubiquitous
presence
across
divergent
phylogenies
including
all
highest
priority
pathogens
Candida
albicans,
auris,
Aspergillus
fumigatus
Cryptococcus
neoformans.
We
then
biochemically
characterized
two
representative
from
C.
albicans
demonstrating
exceptionally
efficient
splicing
catalysis
relative
previously-characterized
introns.
Indeed,
intron
displays
extremely
rapid
catalytic
turnover,
even
at
ambient
temperatures
physiological
magnesium
ion
concentrations.
Our
results
unmask
significant
new
set
players
pathogenic
suggesting
promising
type
target.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Сен. 16, 2024
Systemic
infection
with
Candida
albicans
poses
a
significant
risk
for
people
weakened
immune
systems
and
carries
mortality
rate
of
up
to
60%.
However,
current
therapeutic
options
have
several
limitations,
including
increasing
drug
tolerance,
notable
off-target
effects,
severe
adverse
reactions.
Over
the
past
four
decades,
progress
in
developing
drugs
treat
infections
has
been
sluggish.
This
comprehensive
review
addresses
limitations
existing
summarizes
efforts
made
toward
redesigning
innovating
or
novel
through
nanotechnology.
The
discussion
explores
potential
applications
nanomedicine
from
perspectives:
nano-preparations
anti-biofilm
therapy,
innovative
formulations
"old
drugs"
targeting
cell
membrane
wall,
reverse
resistance
therapy
subcellular
organelles,
virulence
deprivation
leveraging
unique
polymorphism
albicans.
These
approaches
are
promising
address
above
challenges
enhance
efficiency
development
infections.
By
harnessing
nano-preparation
technology
transform
preclinical
drugs,
targets
will
be
uncovered,
providing
effective
solutions
broader
horizons
improve
patient
survival
rates.
Frontiers in Cellular and Infection Microbiology,
Год журнала:
2025,
Номер
15
Опубликована: Апрель 16, 2025
Fungal
infections
are
becoming
more
prevalent
globally,
particularly
affecting
immunocompromised
populations,
such
as
people
living
with
HIV,
organ
transplant
recipients
and
those
on
immunomodulatory
therapy.
Globally,
approximately
6.55
million
affected
by
invasive
fungal
annually,
leading
to
serious
health
consequences
death.
Mitochondria
membrane-bound
organelles
found
in
almost
all
eukaryotic
cells
play
an
important
role
cellular
metabolism
energy
production,
including
pathogenic
fungi.
These
possess
their
own
genome,
the
mitochondrial
which
is
usually
circular
encodes
proteins
essential
for
production.
Variation
evolutionary
adaptation
within
between
species'
genomes
can
affect
function,
consequently
production
metabolic
activity,
may
contribute
pathogenicity
drug
resistance
certain
species.
This
review
explores
link
genome
mechanisms
of
resistance,
a
particular
focus
Cryptococcus
neoformans
Candida
albicans.
insights
deepen
our
understanding
biology
provide
new
avenues
developing
innovative
therapeutic
strategies.
Microbiology and Molecular Biology Reviews,
Год журнала:
2024,
Номер
88(3)
Опубликована: Сен. 4, 2024
SUMMARY
The
ability
to
overcome
metabolic
stress
is
a
major
determinant
of
outcomes
during
infections.
Pathogens
face
nutrient
and
oxygen
deprivation
in
host
niches
their
encounter
with
immune
cells.
Immune
cells
require
adaptations
for
producing
antimicrobial
compounds
mounting
antifungal
inflammation.
Infection
also
triggers
systemic
changes
organ
metabolism
energy
expenditure
that
range
from
an
enhanced
produce
robust
response
reduced
as
infection
progresses,
which
coincides
dysfunction.
Competition
nutrients
between
hosts
pathogens
means
successful
survival
recovery
balance
elimination
the
pathogen
by
systems
(resistance),
doing
so
minimal
damage
tissues
organs
(tolerance).
Here,
we
discuss
our
current
knowledge
pathogen,
cell
fungal
infections,
impact
disorders,
such
obesity
diabetes.
We
put
forward
idea
that,
while
use
regulation
proliferation
responses
(i.e.,
resistance)
has
been
growing
over
years,
need
study
mechanisms
control
tolerance
pathogens.
A
comprehensive
understanding
how
resistance
interventions
may
provide
insights
into
therapeutic
strategies
could
be
used
adjunctly
drugs
improve
patient
outcomes.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(10), С. 5209 - 5209
Опубликована: Май 10, 2024
Mycoses
are
one
of
the
major
causes
morbidity/mortality
among
immunocompromised
individuals.
Considering
importance
these
infections,
World
Health
Organization
(WHO)
defined
a
priority
list
fungi
for
health
in
2022
that
include
Candida
albicans
as
belonging
to
critical
group
and
Pichia
kudriavzevii
(Candida
krusei)
medium
group.
The
existence
few
available
antifungal
drugs,
their
high
toxicity,
acquired
fungal
resistance,
appearance
new
species
with
broader
spectrum
points
out
need
searching
antifungals,
preferably
multiple
mechanisms
action.
cyclam
salt
H4[H2(4-CF3PhCH2)2Cyclam]Cl4
was
previously
tested
against
several
revealed
an
interesting
activity,
minimal
inhibitory
concentration
(MIC)
values
8
µg/mL
C.
krusei
128
albicans.
main
objective
present
work
deeply
understand
involved
its
activity.
effects
on
yeast
metabolic
viability
(resazurin
reduction
assay),
mitochondrial
function
(JC-1
probe),
production
reactive
oxygen
(DCFH-DA
probe)
intracellular
ATP
levels
(luciferin/luciferase
assay)
were
evaluated.
induced
significant
decrease
activity
both
krusei,
increase
Reactive
Oxygen
Species
(ROS)
production,
impaired
function.
latter
observed
by
depolarization
membrane
levels,
seems
be
H4[H2(4-CF3PhCH2)2Cyclam]Cl4.
interference
human
cells
CC50
value
HEK-293
embryonic
kidney
1.1
μg/mL
HC10
red
blood
0.8
μg/mL.
