International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3779 - 3779
Опубликована: Апрель 17, 2025
The
emergence
of
multidrug-resistant
and
extensively
drug-resistant
Mycobacterium
tuberculosis
strains
poses
serious
challenges
to
global
control,
highlighting
the
urgent
need
elucidate
mechanisms
underlying
multidrug
resistance.
In
this
study,
we
screened
for
spontaneous
bortezomib
(BTZ)-resistant
smegmatis
(Msm)
mutants
identified
a
strain,
Msm-R1-2,
exhibiting
16-
64-fold
increases
in
minimum
inhibitory
concentrations
(MICs)
BTZ
linezolid
(LZD),
respectively,
compared
parental
strain.
Whole-genome
sequencing
revealed
resistance-associated
mutations
two
functionally
distinct
genes:
MSMEG_1380,
encoding
transcriptional
regulator
involved
efflux
pump
expression,
MSMEG_0965,
porin
protein.
CRISPR-Cpf1-assisted
gene
knockout
editing
experiments
confirmed
that
single
either
MSMEG_1380
or
MSMEG_0965
caused
low-level
resistance
(4-fold
MIC
increase)
LZD,
while
dual
conferred
levels
comparable
with
MICs
respectively.
An
ethidium
bromide
accumulation
assay
demonstrated
reduce
cell
wall
permeability,
contributing
Furthermore,
quantitative
real-time
PCR
showed
upregulate
mmpS5-mmpL5
system.
Together,
these
function
synergistically:
restricted
drug
entry
combined
enhanced
confers
robust
These
findings
provide
novel
insights
into
evolutionary
mycobacteria.
Antibiotics,
Год журнала:
2024,
Номер
13(8), С. 746 - 746
Опубликована: Авг. 9, 2024
Antibiotic
resistance
emerged
shortly
after
the
discovery
of
first
antibiotic
and
has
remained
a
critical
public
health
issue
ever
since.
Managing
in
clinical
settings
continues
to
be
challenging,
particularly
with
rise
superbugs,
or
bacteria
resistant
multiple
antibiotics,
known
as
multidrug-resistant
(MDR)
bacteria.
This
rapid
development
compelled
researchers
continuously
seek
new
antimicrobial
agents
curb
resistance,
despite
shrinking
pipeline
drugs.
Recently,
focus
shifted
plants,
fungi,
lichens,
endophytes,
various
marine
sources,
such
seaweeds,
corals,
other
microorganisms,
due
their
promising
properties.
For
this
review,
an
extensive
search
was
conducted
across
scientific
databases,
including
PubMed,
Elsevier,
ResearchGate,
Scopus,
Google
Scholar,
encompassing
publications
from
1929
2024.
review
provides
concise
overview
mechanisms
employed
by
develop
followed
in-depth
exploration
plant
secondary
metabolites
potential
solution
MDR
pathogens.
In
recent
years,
interest
plant-based
medicines
surged,
driven
advantageous
However,
additional
research
is
essential
fully
understand
action
verify
safety
phytochemicals.
Future
prospects
for
enhancing
use
combating
antibiotic-resistant
pathogens
will
also
discussed.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 13, 2025
Pulmonary
macrophages
undergo
dynamic
changes
in
population,
proportion,
and
polarization
during
respiratory
diseases.
Monitoring
these
is
critical
for
understanding
their
roles
pathology,
improving
the
diagnosis,
guiding
drug
development.
However,
current
analytic
methods
based
on
tissue
biopsy
are
invasive
static,
limiting
ability
to
provide
such
information.
Herein,
we
report
a
dual-locked
macrophage-specific
renal-clearable
probe
(DMRPNOCas)
monitoring
of
pulmonary
influenza
A
virus
(IAV)
infection.
DMRPNOCas
activates
fluorescence
presence
two
biomarkers
(caspase-1
NO)
only
coexpressed
by
M1
macrophages.
To
optimize
NO
reactivity,
scaffold
screened
from
hemicyanine
derivatives
with
an
o-phenylenediamine
group
positioned
differently
indole
ring.
Notably,
para-substituted
demonstrates
higher
NO-activated
compared
its
meta-substituted
counterpart.
This
enhancement,
as
revealed
quantum
chemical
calculations,
attributed
differential
inhibition
twisted
intramolecular
charge
transfer
induced
reaction.
specifically
distinguishes
other
leukocytes
including
T
cells,
neutrophils,
M2
macrophages,
capability
unmatched
single-locked
control
probes
reported
probes.
Consequently,
enables
vivo
uncovering
extensive
recruitment
monocyte-derived
within
48
h
IAV
process
accompanied
significant
reduction
alveolar
These
findings
new
insights
into
macrophage-mediated
inflammation
underscore
potential
precise
diagnosis
pathological
processes.
Microbiology Spectrum,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 26, 2025
ABSTRACT
The
escalating
threat
of
mycobacterial
infectious
diseases,
particularly
those
caused
by
nontuberculous
mycobacteria
(NTM),
poses
a
serious
challenge
to
public
health.
Linezolid
(LZD),
an
oxazolidinone
antimicrobial,
exhibits
potent
activity
against
Mycobacterium
tuberculosis
and
NTM.
Generally,
mutations
in
the
rrl
rplC
genes
are
widely
associated
with
resistance
LZD.
However,
this
study,
we
screened
marinum
strains
lacking
such
mutations,
indicating
presence
alternative
mechanism.
Notably,
through
whole-genome
sequencing,
identified
novel
mutation
C395T
MMAR_0911
(
grcC1
)
gene
that
has
never
been
linked
drug
resistance.
This
leads
A132V
substitution
encoded
protein,
polyprenyl
diphosphate
synthase
potentially
involved
synthesis
cell
wall
components
menaquinones.
We
found
overexpression
multiple
drugs
including
LZD,
clarithromycin
(CLR),
vancomycin
(VAN),
clofazimine
(CFZ),
rifampicin
(RIF),
cefoxitin
(CEF),
levofloxacin
(LEV),
moxifloxacin
(MXF)
reduced
permeability,
while
silence
knockout
showed
increased
permeability
susceptibility
these
drugs.
Using
CRISPR/Cpf1-assisted
editing,
confirmed
conferred
low-level
aforementioned
abscessus
smegmatis
.
Furthermore,
thin-layer
chromatography
analysis
indicated
glycolipid
polarity
mutant
strains,
suggesting
impact
on
envelope
integrity.
Our
findings
suggest
GrcC1
contributes
reducing
highlighting
its
potential
as
target
for
antimicrobial
agents
diagnostic
marker.
IMPORTANCE
study
uncovers
mechanism
mycobacteria,
focusing
previously
uncharacterized
gene.
new
mutation,
A132V,
GrcC1,
which
is
component
menaquinone
production.
not
only
linezolid
but
also
broad
range
drugs,
clarithromycin,
vancomycin,
rifampicin.
Through
advanced
techniques
like
CRISPR
interference
demonstrated
plays
critical
role
across
species.
These
represent
first
connection
between
resistance,
offering
insights
into
combating
infections
(NTM).
work
highlights
therapeutic
approaches
marker
drug-resistant
NTM
infections.
Capreomycin
(CMN)
paired
with
levofloxacin
(LEV)
was
tested
in
patients
multidrug-resistant
pulmonary
tuberculosis
(MDR-PTB)
for
efficacy
and
immune
function.
The
control
group
(40
cases)
received
conventional
treatment
the
observation
CMN
combined
LEV
were
established.
Three
months
of
intensification
therapy
eighteen
consolidation
performed.
therapeutic
effects
(sputum
negative
conversion,
lesion
absorption,
cavity
shrinkage,
total
effective
rates),
CD4+,
CD8+,
immunoglobulin
A
(IgA),
IgM,
IgG,
interleukin-6
(IL-6),
IL-17,
tumor
necrosis
factor-α
(TNF-α),
serum
alkaline
phosphatase
(ALP),
aspartate
aminotransferase
(ALT),
alanine
(AST)
assessed.
Adverse
reactions
compared.
After
treatment,
performed
at
a
higher
sputum
conversion
rate,
absorption
shrinkage
rate
than
group;
IgA,
IL-17
increased
IL-6,
TNF-α
decreased
both
groups,
all
them
improved
significantly
ALP,
ALT,
AST
elevated
but
differences
between
groups
comparable.
is
highly
MDR-PTB
patients,
enhancing
function
reducing
inflammation
while
having
minimal
on
liver
Infection and Drug Resistance,
Год журнала:
2025,
Номер
Volume 18, С. 1425 - 1437
Опубликована: Март 1, 2025
A
hospital
in
Xi'an,
Shaanxi
Province,
China,
implemented
patient-centered
care
services
to
improve
the
treatment
outcomes
of
patients
with
multidrug-resistant/rifampicin-resistant
tuberculosis.
Given
high
recurrence
rate
and
challenges
this
disease,
study
aimed
evaluate
effects
compared
standard
improving
patient
adherence
reducing
loss
follow-up.
This
single-center
retrospective
cohort
included
tuberculosis
diagnosed
treated
at
Xi'an
Tuberculosis
Prevention
Treatment
Hospital
from
January
2018
December
2019.
Descriptive
statistics,
survival
analysis,
multivariate
Cox
regression
analysis
were
used
analyze
impact
on
adherence.
Data
collection
patients'
demographic
characteristics,
clinical
data,
outcomes,
reasons
for
total
429
final
166
standard-of-care
group
263
group.
The
success
(86.3%)
was
significantly
higher
than
(59.0%),
follow-up
lower
(6.8%
vs
30.1%).
Multivariate
showed
that
reduced
risk
(adjusted
odds
ratio
0.14).
main
economic
difficulties,
lack
knowledge,
inadequate
social
support.
model
improved
patients,
demonstrating
potential
benefits
managing
drug-resistant
Based
these
findings,
exploring
optimizing
other
high-burden
areas
is
recommended
enhance
overall
quality
life
patients.
Pharmaceutics,
Год журнала:
2024,
Номер
16(6), С. 818 - 818
Опубликована: Июнь 17, 2024
Multidrug-resistant
tuberculosis
(MDR-TB)
is
a
global
health
concern.
Standard
treatment
involves
the
use
of
linezolid,
repurposed
oxazolidinone.
It
associated
with
severe
adverse
effects,
including
myelosuppression
and
mitochondrial
toxicity.
As
such,
it
imperative
to
identify
novel
alternatives
that
are
better
tolerated
but
equally
or
more
effective.
Therefore,
this
review
aims
explore
alternative
oxazolidinones
potentially
replace
linezolid
in
management
TB.
The
keywords
were
searched
PubMed
eligible
compounds.
individual
drug
compounds
then
term
relevant
vitro,
vivo
clinical
studies.
search
identified
sutezolid,
tedizolid,
delpazolid,
eperezolid,
radezolid,
contezolid,
posizolid
TBI-223,
addition
linezolid.
An
additional
resulted
32
preclinical
21
All
except
eperezolid
positive
outcomes.
Sutezolid
delpazolid
completed
early
phase
2
studies
safety
equal
superior
efficacy.
Linezolid
expected
continue
as
mainstay
therapy,
renewed
interest
monitoring.
Sutezolid,
TBI-223
displayed
promising
preliminary
results.
Further
would
be
required
assess
profiles
optimize
dosing
regimens.
Reviews in Inorganic Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 29, 2024
Abstract
Enticed
by
the
present
scenario
of
infectious
diseases,
four
new
Co(II),
Ni(II),
Cu(II),
and
Cd(II)
complexes
Schiff
base
ligand
were
synthesized
from
6,6′-((1E-1′E)(phenazine-2,3-dielbis(azanylidene)-bis-(methanylidene)-bis-(3-(diethylamino)phenol))
(
H
2
L
)
to
ascertain
as
effective
drug
for
antituberculosis,
anti-inflammatory,
antioxidant,
cytotoxic
antimicrobial
activities.
The
organic
its
metal(II)
characterized
numerous
physical
spectroscopic
methods,
which
showed
that
have
a
general
formula,
[
ML
],
(where
M
=
Co(II)
C1
),
Ni(II)
C2
Cu(II)
C3
C4
)),
metal
been
proposed
square
planar
geometry,
are
amorphous
in
nature,
thermally
stable.
Data
highlight
obtained
activity
testing
against
tuberculosis,
inflammation,
oxidants
all
compounds
significantly
active
these
symptoms.
Also,
was
evaluate
effectiveness
various
bacterial
fungal
strains.
Specifically,
strains
Bacillus
subtilis
,
Staphylococcus
aureus
Escherichia
coli
Pseudomonas
aeruginosa
two
Aspergillus
flavus
Candida
albicans
tested
compared
results
some
standard
drugs.
revealed
compound
more
than
comparison
In
addition,
found
be
most
antibiotics
fungi,
while
other
moderate
antifungal
activity.
Moreover,
support
vitro
results,
certain
computational
studies
molecular
docking
studies,
DFT,
MESP,
AMEDT
also
conducted
confirm
an
tuberculosis.
These
is
tuberculosis
has
desirable
effects
such
absorption,
no
degradation
hepatotoxicity,
etc.