Hybrid Molecules of Benzothiazole and Hydroxamic Acid as Dual-Acting Biofilm Inhibitors with Antibacterial Synergistic Effect against Pseudomonas aeruginosa Infections
Z. Zhang,
No information about this author
Siyu Zhao,
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Wen-Qian Liu
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et al.
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 13, 2025
The
ubiquitous
opportunistic
pathogen
Pseudomonas
aeruginosa
(P.
aeruginosa)
causes
biofilm-associated
drug-resistant
infections
that
often
lead
to
treatment
failure.
Targeting
the
bacterium's
quorum
sensing
(QS)
and
iron
homeostasis
presents
a
promising
strategy
combat
biofilm
formation.
This
study
synthesized
benzothiazole-conjugated
hydroxamic
acid
derivatives
as
dual-acting
inhibitors,
compound
JH21
was
identified
hit
with
potent
submicromolar
inhibitory
activity
(IC50
=
0.4
μM).
Further
mechanistic
studies
demonstrated
not
only
production
of
virulence
decreased
through
mainly
inhibiting
QS
system
but
also
competed
for
high-affinity
siderophore
pyoverdine,
inducing
deficiency
biofilm.
Moreover,
significantly
enhanced
efficacy
tobramycin
ciprofloxacin
by
200-
1000-fold,
respectively,
in
mouse
wound
infection
model.
These
results
emphasized
feasibility
inhibitors
against
resistant
P.
potential
novel
antibacterial
synergist.
Language: Английский
A guide to publishing in Biofilm: how to avoid a desk rejection
Biofilm,
Journal Year:
2025,
Volume and Issue:
unknown, P. 100282 - 100282
Published: April 1, 2025
Language: Английский
Integrated transcriptomics and metabolomics study on the biofilm formation of Haemophilus influenzae by the stimulation of amoxicillin-clavulanate at subinhibitory concentration
Microbial Pathogenesis,
Journal Year:
2025,
Volume and Issue:
205, P. 107650 - 107650
Published: April 29, 2025
Language: Английский
Conformational change as a mechanism for toxin activation in bacterial toxin-antitoxin systems
Journal of Virology,
Journal Year:
2024,
Volume and Issue:
98(11)
Published: Oct. 24, 2024
ABSTRACT
Toxin/antitoxin
(TA)
systems
are
present
in
nearly
every
prokaryotic
genome
and
play
the
important
physiological
roles
of
phage
inhibition
by
reducing
metabolism
(this
includes
persistence
for
extreme
case
complete
cessation
metabolism),
genetic
element
stabilization,
biofilm
formation.
TA
have
also
been
incorporated
into
other
cell
systems,
such
as
CRISPR-Cas
quorum
sensing.
For
simplest
best-studied
case,
proteinaceous
toxins
antitoxins
(i.e.,
type
II),
toxin
activity
is
masked
direct
binding
antitoxin.
A
long-standing,
unresolved
question
field
how
activated
when
bound
to
at
nanomolar
affinity.
The
current
paradigm
envisions
preferential
degradation
antitoxin
a
protease,
but
this
highly
unlikely
that
protease
cannot
discriminate
between
because
both
structured.
Strikingly,
recent
results
from
several
studies
show
one
likely
mechanism
activation
conformational
changes
complex
result
release
or
protein
trigger,
phages,
thermally-driven
refolding
dynamics.
Language: Английский
The battle against dental caries: defeating biofilm formed by bacterial isolates using vanillin and plant essential oils: in vitro and ex vivo approaches
Manar M. Ahmed,
No information about this author
Nehal Yousef,
No information about this author
Momen Askoura
No information about this author
et al.
Future Journal of Pharmaceutical Sciences,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: Oct. 25, 2024
Abstract
Background
Infections
caused
by
biofilm-forming
bacteria
have
significantly
linked
to
dental
plaque
and
caries.
The
aim
of
this
study
is
assess
efficacy
some
natural
compounds
in
inhibition
eradication
biofilm
formed
bacterial
isolates
from
infections.
Results
Bacterial
were
recovered
plaque/caries
identified
using
standard
microbiological
tests
16S
rDNA
sequencing.
isolated
strains
include
Staphylococcus
aureus
,
epidermidis
Enterococcus
faecalis
Klebsiella
pneumoniae
Escherichia
coli
.
antibiotic
susceptibility
was
determined
disk
diffusion
method
revealed
that
the
majority
showed
high
resistance,
61%
found
be
multidrug
resistant.
formation
capacity
investigated
microtiter
plate
assay.
Among
77
isolates,
seventeen
moderate
capacity,
twenty-two
near-moderate,
thirty-four
had
weak
four
non-biofilm
producers.
antibiofilm
activity
tested
(rose
jasmine
oils,
propolis,
vanillin,
vinegar)
evaluated
against
with
highest
capacity.
vitro
ability
substances
alone
or
combination
each
other
evaluate
their
prevent
destroy
preformed
single-/multispecies
biofilms.
Finally,
ex
vivo
on
teeth.
Our
results
vanillin
rose
oils
promising
activities
both
models.
Conclusions
Dental
caries
can
successfully
prevented
these
incorporated
new
anticaries
formulations.
Language: Английский