Antibiotics,
Journal Year:
2025,
Volume and Issue:
14(5), P. 423 - 423
Published: April 22, 2025
Background/Objectives:
Multidrug-resistant
Gram-negative
ESKAPE
pathogens,
including
E.
coli,
K.
pneumoniae,
P.
aeruginosa,
and
A.
baumannii,
pose
a
significant
global
health
threat.
Gramicidin
S,
potent
cyclic
antimicrobial
peptide,
is
largely
ineffective
against
these
bacteria,
its
high
haemolytic
toxicity
limits
clinical
usage.
This
study
reports
on
several
novel
gramicidin
S
analogues
with
improved
efficacy
safety
profiles
multidrug-resistant
bacteria.
Methods:
A
total
of
19
derivatives
were
synthesised
using
Fmoc-based
solid-phase
peptide
synthesis
targeted
substitutions
to
enhance
cationicity
modulate
hydrophobicity.
Minimum
inhibitory
concentrations
(MICs)
determined
standard
Gram-positive
strains.
Haemolytic
in
vitro
nephrotoxicity
evaluated
human
red
blood
cells
HEK-293
cells,
respectively.
All
peptides
characterised
by
RP-HPLC
HRMS.
Results:
The
selective
incorporation
DArg
Trp
significantly
enhanced
activity
bacteria
while
reducing
cytotoxicity.
Peptide
8
the
therapeutic
index
(TI)
coli
10-fold
(MIC:
µg/mL;
TI:
4.10)
compared
32
0.38).
9
exhibited
an
8-fold
potency
increase
pneumoniae
25-fold
TI
improvement.
aeruginosa
over
7
showed
27-fold
enhancement.
active
retained
broad-spectrum
S.
aureus,
MRSA.
Conclusions:
findings
highlight
critical
role
balancing
hydrophobicity
overcome
species-specific
resistance
mechanisms.
Our
demonstrate
reduced
parent
providing
robust
platform
for
development
new
antibiotics
bacterial
pathogens.
BMC Genomic Data,
Journal Year:
2025,
Volume and Issue:
26(1)
Published: Jan. 22, 2025
Pseudomonas
aeruginosa,
a
Gram-negative
opportunistic
pathogen,
is
frequently
associated
with
multidrug
resistance
and
global
epidemic
outbreaks,
contributing
significantly
to
morbidity
mortality
in
hospitalized
patients.
However,
P.
aeruginosa
belonging
the
sequence
type
(ST)
16
was
rarely
reported.
Here,
this
report
presents
complete
genome
of
YK01,
ST16
isolate
from
patient
keratitis.
The
reference
YK01
expected
provide
valuable
data
for
investigating
its
genomic
population,
enhancing
understanding
genetic
basis
species
complex.
A
6.3
Mb
obtained
by
combining
Illumina
150-bp
short
reads
Nanopore
long
reads.
assembly
fully
chromosomal
size
6,183,266
bp,
presenting
GC
content
66.7%,
plasmid
46,067
59.0%.
Predicted
features
include
5,709
CDS,
12
rRNAs,
63
tRNAs,
4
ncRNAs,
5,788
genes.
To
our
knowledge,
represents
first
ST16,
providing
crucial
information
further
comparative
analysis.
Veterinary Sciences,
Journal Year:
2025,
Volume and Issue:
12(2), P. 157 - 157
Published: Feb. 11, 2025
The
isolation
of
multidrug-resistant
(MDR)
bacteria
from
the
urinary
tracts
pets
is
increasingly
common,
particularly
in
animals
with
concurrent
health
conditions.
Pseudomonas
aeruginosa
(PA)
one
most
significant
antimicrobial-resistant
affecting
cats
and
dogs
within
European
Union
(EU).
This
study
aims
to
review
prevalence
antimicrobial
resistance
patterns
PA
isolated
urine
samples
small
globally.
pathogen
known
for
its
opportunistic
infections
a
concern
veterinary
medicine
due
inherent
multiple
antibiotics
ability
acquire
additional
mechanisms.
seeks
enhance
educational
initiatives
regarding
management
emerging
MDR
bacteria.
PeerJ,
Journal Year:
2025,
Volume and Issue:
13, P. e18986 - e18986
Published: Feb. 24, 2025
Pseudomonas
aeruginosa
continues
to
be
a
significant
contributor
high
morbidity
and
mortality
rates
worldwide,
particularly
due
its
role
in
severe
infections
such
as
hospital-acquired
conditions,
including
ventilator-associated
pneumonia
various
sepsis
syndromes.
The
global
increase
antimicrobial-resistant
(AMR)
P.
strains
has
made
these
more
difficult
treat,
by
limiting
the
effective
drug
options
available.
This
systematic
review
meta-analysis
aim
provide
an
updated
summary
of
prevalence
AMR
over
past
5
years.
A
search
was
performed
across
three
major
electronic
databases—PubMed,
ScienceDirect,
Web
Science—yielding
40
eligible
studies
published
between
2018
2023.
Using
random-effects
model,
our
estimated
that
overall
Asia
Africa
years
22.9%
(95%
CI
[14.4–31.4]).
for
multidrug-resistant
(MDR)
extensively
drug-resistant
(XDR)
were
found
46.0%
[37.1–55.0])
19.6%
[4.3–34.9]),
respectively.
Furthermore,
extended-spectrum
β-lactamase-
metallo-β-lactamase-producing
33.4%
[23.6–43.2])
16.0%
[9.8–22.3]),
Notably,
resistance
β-lactams
used
treating
pseudomonal
alarmingly
high,
with
84.4%
100.0%
cephalosporins,
40%
isolates
showed
penicillins.
Our
analysis
identified
lowest
last-resort
antimicrobials,
0.3%
[0.0–1.3])
polymyxin
B
5.8%
[1.5–10.2])
colistin/polymyxin
E.
low
polymyxins
suggest
antibiotics
remain
against
MDR
.
However,
findings
also
highlight
critical
public
health
threat
posed
,
concerning
β-lactam
antibiotics.
underscores
need
carefully
planned
intervention
strategies,
development
new
address
growing
challenge
resistance.
Developing
robust
antibiotic
treatment
protocols
is
essential
better
management
control
globally.
Therefore,
continued
research
international
collaboration
vital
tackle
this
escalating
challenge.
study
protocol
registered
International
Prospective
Register
Systematic
Reviews
(PROSPERO),
under
registration
number
CRD42023412839.
Antibiotics,
Journal Year:
2025,
Volume and Issue:
14(1), P. 30 - 30
Published: Jan. 3, 2025
Background/Objectives:
Pseudomonas
aeruginosa
rapidly
acquires
antibiotic
resistance
and
demonstrates
increasing
tolerance
to
antiseptics.
This
study
evaluated
the
activity
of
eight
antiseptics
against
P.
aeruginosa,
assessed
its
ability
develop
adaptation
these
antiseptics,
and,
for
first
time,
determined
Karpinski
Adaptation
Index
(KAI)
this
bacterium.
Methods:
The
minimal
inhibitory
concentration
(MIC),
susceptibility
antibiotics,
bactericidal
time
according
EN
1040:2005,
potential,
KAI
strains
were
evaluated.
Results:
most
effective
based
on
MIC
activity,
octenidine
dihydrochloride
(OCT;
mean
11.3
±
4.5
µg/mL),
polyhexamethylene
biguanide
(PHMB;
22.6
8.0
chlorhexidine
digluconate
(CHX;
26.6
14.4
µg/mL).
Sodium
hypochlorite
(NaOCl)
ethacridine
lactate
(ET)
showed
moderate
while
boric
acid
(BA),
povidone-iodine
(PVI),
potassium
permanganate
(KMnO4)
exhibited
weakest
activity.
values
NaOCl
(95
15.4
µg/mL)
KMnO4
(>10
mg/mL)
close
or
exceeded
clinical
concentrations
used
in
commercial
products.
OCT,
CHX,
PVI
fastest
effect
within
1
min.
Bactericidal
times
up
15
min
PHMB,
60
ET,
more
than
BA,
NaOCl,
KMnO4.
lowest
values,
indicating
a
low
risk,
observed
OCT
(0.12),
PHMB
(0.19),
BA
(0.19).
Moderate
risk
was
noted
(0.21),
CHX
(0.29),
ET
(0.47).
highest
signifying
very
high
found
(1.0)
(≥1.0).
Conclusions:
Antiseptics
like
partially
can
be
critical
quick
antibacterial
action
infected
wounds,
agents
such
as
might
reserved
cases
where
prolonged
contact
are
possible.
Given
rapid
currently
use,
reconsideration
their
effectiveness
treating
skin
mucous
membrane
infections
is
recommended.
Marine Drugs,
Journal Year:
2025,
Volume and Issue:
23(1), P. 43 - 43
Published: Jan. 16, 2025
The
rise
in
multidrug-resistant
(MDR)
bacteria
has
prompted
extensive
research
into
antibacterial
compounds,
as
these
resistant
strains
compromise
current
treatments.
This
resistance
leads
to
prolonged
hospitalization,
increased
mortality
rates,
and
higher
healthcare
costs.
To
address
this
challenge,
the
pharmaceutical
industry
is
increasingly
exploring
natural
products,
particularly
those
of
marine
origin,
promising
candidates
for
antimicrobial
drugs.
Marine
sponges,
particular,
are
interest
because
their
production
secondary
metabolites
(SM),
which
serve
chemical
defenses
against
predators
pathogens.
These
exhibit
a
wide
range
therapeutic
properties,
including
activity.
systematic
review
examines
recent
advancements
identifying
new
sponge-derived
compounds
with
activity,
specifically
targeting
Pseudomonas
aeruginosa,
prevalent
Gram-negative
pathogen
highest
incidence
rates
clinical
settings.
selection
criteria
focused
on
reported
Minimum
Inhibitory
Concentration
(MIC)
values.
identified
SM
include
alkaloids,
sesterterpenoids,
nitrogenous
diterpene,
bromotyrosine-derived
derivatives.
structural
features
active
selected
may
provide
foundational
framework
developing
new,
highly
bioactive
agents.
Infectious Medicine,
Journal Year:
2025,
Volume and Issue:
4(1), P. 100168 - 100168
Published: Feb. 6, 2025
Phages,
including
the
viruses
that
lyse
bacterial
pathogens,
offer
unique
therapeutic
advantages,
their
capacity
to
antibiotic-resistant
bacteria
and
disrupt
biofilms
without
harming
host
microbiota.
The
lack
of
new
effective
antibiotics
growing
limitations
existing
have
refocused
attention
on
phage
therapy
as
an
option
in
complex
clinical
cases
such
burn
wounds,
cystic
fibrosis,
pneumonia.
This
review
describes
preclinical
studies
which
has
been
both
human
veterinary
medicine,
agricultural
context.
In
addition,
critical
challenges,
narrow
range
bacteriophages,
possibility
resistance,
regulatory
constraints
widespread
use
therapy,
are
addressed.
Future
directions
include
optimizing
through
strategies
ranging
from
cocktails
broadening
genetic
modification,
using
phages
vaccines
or
biocontrol
agents.
future,
if
can
be
efficiently
delivered,
maintained
a
stable
state,
phage-antibiotic
synergy
achieved,
will
much
needed
treatment
options.
However,
successful
implementation
within
current
standards
practice
also
require
considerable
development
infrastructure
greater
public
acceptance.
closing,
this
highlights
promise
backup
substitute
for
antibiotics.
It
proposes
role
significant
adjunct
to,
even
replacement
for,
treating
multidrug-resistant
infections.
Heliyon,
Journal Year:
2025,
Volume and Issue:
11(4), P. e42584 - e42584
Published: Feb. 1, 2025
Pseudomonas
aeruginosa,
a
versatile
and
antibiotic-resistant
gram-negative
pathogen,
poses
critical
threat
to
both
immunocompromised
immunocompetent
populations,
underscoring
the
urgent
need
for
new
therapeutic
targets.
This
study
applies
an
extensive
subtractive
proteomics
approach
identify
viable
drug
targets
within
core
proteome
of
P.
aeruginosa
PAO1,
analyzing
total
5563
proteins.
Through
rigorous,
multi-stage
process,
we
excluded
human
homologs,
identified
essential
proteins,
mapped
functional
pathways,
determined
subcellular
localization,
assessed
virulence
resistance
factors.
comprehensive
analysis
led
identification
three
novel,
druggable
integral
aeruginosa's
pathogenicity
multidrug
resistance:
preprotein
translocase
subunit
SecD,
chemotaxis-specific
methyl
esterase,
imidazole
glycerol
phosphate
synthase
HisF2.
Following
this,
inverse
virtual
screening
464,867
compounds
from
VITAS-M
library,
performed
using
Schrödinger's
Glide
module,
initially
pinpointed
15
potent
hits
with
favorable
binding
affinities
pharmacokinetic
profiles
as
confirmed
by
QikProp
analysis.
Subsequent
molecular
dynamics,
MMPBSA
DFT
calculations
refined
these
promising
candidates:
STK417467
HisF2,
STL321396
methylesterase,
STL243336
SecD.
These
show
strong
potential
inhibitors
could
be
developed
further
agents
against
multidrug-resistant
infections.
provides
robust
computational
framework
discovery
candidate
inhibitors,
marking
significant
step
toward
effective
treatments
resistant