Arsenic-Induced Modulation of Virulence and Drug Resistance in Pseudomonas aeruginosa
Journal of Hazardous Materials,
Journal Year:
2025,
Volume and Issue:
488, P. 137352 - 137352
Published: Jan. 24, 2025
Language: Английский
In Vitro and In Vivo Evaluation of the De Novo Designed Antimicrobial Peptide P6.2 Against a KPC-Producing P. aeruginosa Clinical Isolate
Melina Martínez,
No information about this author
Merlina Corleto,
No information about this author
Melanie Weschenfeller
No information about this author
et al.
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(3), P. 339 - 339
Published: Feb. 27, 2025
The
antimicrobial
peptide
P6.2
was
previously
de
novo
designed
as
an
alpha
helix
cationic
amphipathic
molecule.
In
previous
work,
we
have
shown
that
this
displayed
significant
activity
against
both
Gram-positive
(Staphylococcus
aureus)
and
Gram-negative
(Pseudomonas
aeruginosa)
bacteria.
However,
while
lacked
biofilm-inhibiting
properties
the
P.
aeruginosa
strain
PA01,
it
anti-inflammatory
effects
in
a
murine
acute
lung
infection
model
challenged
with
pathogen.
its
possible
synergy
meropenem
were
evaluated
vitro
vivo
using
Galleria
mellonella
carbapenem-resistant
KPC-producing
clinical
isolate
of
aeruginosa.
Firstly,
cytotoxic
effect
on
A549
RAW264.7
cell
lines
assayed,
showing
no
cytotoxicity
at
64
µg/mL
below.
Then,
MIC
(minimal
inhibitory
concentration)
bactericidal
carbapenemase-producing
M13513
determined.
showed
between
32
µg/mL,
rapid
(less
than
45
min).
stability
different
temperatures
bovine
serum
37
°C
also
analyzed,
good
almost
degradation
after
15
min
incubation
100
or
24
h
serum,
respectively.
antibiofilm
evaluated,
although
did
not
show
biofilm
activity,
demonstrate
disruptive
together
inside
pre-formed
biofilm.
synergistic
carbapenem
then
analyzed
by
killing
kinetics,
revealing
interaction
antibiotic
strain.
Finally,
larvae
model.
Interestingly,
G.
mellonella,
alone
completely
clear
caused
M13513.
when
combined
meropenem,
demonstrated
effect,
leading
to
increased
survival
rates
infected
larvae.
results
presented
here
highlight
potential
displays
used
combination
carbapenems
clinically
relevant
Language: Английский
Revealing the impact of Pseudomonas aeruginosa quorum sensing molecule 2'-aminoacetophenone on human bronchial-airway epithelium and pulmonary endothelium using a human airway-on-a-chip
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 24, 2025
Abstract
Pseudomonas
aeruginosa
(PA)
causes
severe
respiratory
infections
utilizing
multiple
virulence
functions.
Our
previous
findings
on
PA
quorum
sensing
(QS)-regulated
small
molecule,
2’-aminoacetophenone
(2-AA),
secreted
by
the
bacteria
in
infected
tissues,
revealed
its
effect
immune
and
metabolic
functions
favouring
a
long-term
presence
of
host.
However,
studies
2-AA’s
specific
effects
bronchial-airway
epithelium
pulmonary
endothelium
remain
elusive.
To
evaluate
2AA’s
spatiotemporal
changes
human
airway,
considering
endothelial
cells
as
first
point
contact
when
route
lung
infection
is
hematogenic,
we
utilized
microfluidic
airway-on-chip
lined
polarized
endothelium.
Using
this
platform,
performed
RNA-sequencing
to
analyse
responses
2-AA-treated
primary
microvascular
(HPMEC)
adjacent
normal
bronchial
epithelial
(NHBE)
from
healthy
female
donors
potential
cross-talk
between
these
cells.
Analyses
unveiled
signaling
biosynthesis
pathways
be
differentially
regulated
2-AA
cells,
including
HIF-1
pyrimidine
signaling,
glycosaminoglycan,
glycosphingolipid
biosynthesis,
while
were
fatty
acid
metabolism,
phosphatidylinositol
estrogen
receptor
proinflammatory
pathways.
Significant
overlap
both
cell
types
response
was
found
genes
implicated
cellular
In
contrast,
that
related
barrier
permeability,
cholesterol
oxidative
phosphorylation
upon
exposure
studied.
Murine
in-vivo
additional
vitro
culture
confirmed
accumulation
Results
also
biomarkers
associated
with
cystic
fibrosis
idiopathic
modulated
types,
transmembrane
regulator
expression
affected
only
The
2-AA-mediated
within
microphysiological
dynamic
environment
mimicking
airway
enhance
our
understanding
QS
molecule.
This
study
provides
novel
insights
into
their
interactions,
paving
way
for
innovative,
cell-specific
therapeutic
strategies
combat
infections.
Language: Английский
Unveiling the molecular epidemiology of Pseudomonas aeruginosa in lung infections among cystic fibrosis patients in the Brazilian Amazon
BMC Microbiology,
Journal Year:
2025,
Volume and Issue:
25(1)
Published: April 9, 2025
Pseudomonas
aeruginosa
is
a
major
pathogen
in
cystic
fibrosis
(CF),
where
chronic
and
intermittent
infections
significantly
affect
patient
outcomes.
This
study
aimed
to
investigate
the
molecular
epidemiology
of
P.
CF
patients
from
Brazilian
Amazon,
focusing
on
genotypic
diversity,
resistance
profiles,
virulence
factors.
A
cross-sectional
included
72
isolates
44
treated
at
regional
reference
center
between
2018
2019.
Antimicrobial
susceptibility
patterns
were
determined
using
VITEK-2
system
Kirby-Bauer
disk
diffusion.
Virulotypes
defined
by
detection
exoS,
exoU,
exoT,
exoY,
algU,
algD
genes.
Genetic
diversity
was
assessed
multilocus
sequence
typing
(MLST).
Demographic
data,
clinical
severity,
spirometry
results
also
collected.
Among
patients,
54.55%
experienced
infections,
while
45.45%
had
infections.
Chronic
associated
with
older
age,
lower
FEV1,
reduced
Shwachman-Kulczycki
scores.
Multidrug
observed
15.3%
isolates,
particularly
against
ciprofloxacin
piperacillin/tazobactam.
The
exoU
gene
present
55.56%
an
uncommon
finding
populations.
High
genetic
evident,
37
types
(STs),
including
14
novel
STs.
High-risk
clones
(HRCs)
constituted
25%
ST274
being
most
prevalent
(12.5%).
Longitudinal
analysis
revealed
transient
colonization
dominated
stable
clones.
highlights
dynamics
Amazon.
linked
severe
lung
impairment
,
HRCs.
These
findings
underscore
need
for
robust
surveillance
mitigate
burden
Language: Английский
Innate lymphoid cells, immune functional dynamics, epithelial parallels, and therapeutic frontiers in infections
International Reviews of Immunology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 28
Published: April 17, 2025
Innate
lymphoid
cells
(ILCs)
have
emerged
as
pivotal
players
in
the
field
of
immunology,
expanding
our
understanding
innate
immunity
beyond
conventional
paradigms.
This
comprehensive
review
delves
into
multifaceted
world
ILCs,
beginning
with
their
serendipitous
discovery
and
traversing
ontogeny
heterogeneity.
We
explore
distinct
subsets
ILCs
unraveling
intriguing
plasticity,
which
adds
a
layer
complexity
to
functional
repertoire.
As
we
journey
through
activities
address
role
immune
responses
against
various
infections,
categorizing
interactions
helminthic
parasites,
bacterial
pathogens,
fungal
viral
invaders.
Notably,
this
offers
detailed
examination
context
specific
such
Mycobacterium
tuberculosis,
Citrobacter
rodentium,
Clostridium
difficile,
Salmonella
typhimurium,
Helicobacter
pylori,
Listeria
monocytogenes,
Staphylococcus
aureus,
Pseudomonas
aeruginosa,
Influenza
virus,
Cytomegalovirus,
Herpes
simplex
severe
acute
respiratory
syndrome
coronavirus
2.
selection
aimed
for
exploration
infectious
contexts,
opting
microorganisms
based
on
extensive
research
findings
rather
than
considerations
virulence
or
emergence.
Furthermore,
raise
questions
about
potential
resemblances
between
epithelial
cells,
shedding
light
interconnectedness
within
mucosal
microenvironment.
The
culminates
critical
assessment
therapeutic
prospects
targeting
during
infection,
emphasizing
promise
novel
immunotherapeutic
targets.
Nevertheless,
due
recent
evolving
understanding,
effectively
manipulating
is
challenging.
Ensuring
specificity
safety
while
evaluating
long-term
effects
clinical
settings
will
be
crucial.
Language: Английский