Frontiers in Microbiology,
Год журнала:
2023,
Номер
14
Опубликована: Дек. 21, 2023
Staphylococcus
aureus
readily
forms
biofilms
on
host
tissues
and
medical
devices,
enabling
its
persistence
in
chronic
infections
resistance
to
antibiotic
therapy.
The
accessory
gene
regulator
(Agr)
quorum
sensing
system
plays
a
key
role
regulating
S.
biofilm
formation.
This
study
reveals
the
widely
used
fluoroquinolone
antibiotic,
ciprofloxacin,
strongly
stimulates
formation
methicillin-resistant
,
methicillin-sensitive
clinical
isolates
with
diverse
genetic
backgrounds.
Crystal
violet
staining
indicated
that
ciprofloxacin
induced
remarkable
12.46-
15.19-fold
increase
biomass.
Confocal
laser
scanning
microscopy
revealed
denser
biofilms.
Phenotypic
assays
suggest
may
enhance
polysaccharide
intercellular
adhesin
production,
inhibit
autolysis,
reduce
proteolysis
during
development,
thus
promoting
initial
adhesion
enhancing
stability.
Mechanistically,
significantly
alters
expression
of
various
biofilm-related
genes
(
icaA
icaD
fnbA
fnbB
eap
emp
)
regulators
agrA
saeR
).
Gene
knockout
experiments
deletion
agrC
rather
than
saeRS
abolishes
ciprofloxacin-induced
enhancement
formation,
underscoring
.
Thermal
shift
showed
binds
purified
AgrC
protein,
thereby
inhibiting
Agr
system.
Molecular
docking
results
further
support
potential
interaction
between
AgrC.
In
summary,
subinhibitory
concentrations
stimulate
via
an
-dependent
pathway.
inductive
effect
facilitate
local
infection
establishment
bacterial
persistence,
ultimately
leading
therapeutic
failure.
Abstract
Staphylococcus
aureus
is
highly
adapted
to
colonization
of
the
mammalian
host.
In
humans
primary
site
epithelium
nasal
cavity.
A
major
barrier
resident
microbiota,
which
have
mechanisms
exclude
S.
aureus.
As
such,
has
evolved
compete
with
other
bacteria,
one
through
secretion
proteinaceous
toxins.
strains
collectively
produce
a
number
well-characterized
Class
I,
II,
and
IV
bacteriocins
as
well
several
bacteriocin-like
substances,
about
less
known.
These
potent
antibacterial
activity
against
Gram-positive
organisms,
some
also
active
Gram-negative
species.
characterized
date
are
sporadically
produced,
often
encoded
on
plasmids.
More
recently
type
VII
system
(T7SS)
been
shown
play
role
in
interbacterial
competition.
The
T7SS
by
all
isolates
so
may
represent
more
widespread
mechanism
competition
used
this
antagonism
mediated
large
protein
toxins,
three
date:
nuclease
toxin,
EsaD;
membrane
depolarizing
TspA;
phospholipase
TslA.
Further
study
required
decipher
that
these
different
types
secreted
toxins
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Abstract
Staphylococci
utilize
secreted
autoinducing
peptides
(AIPs)
to
regulate
group
behaviour
through
a
process
called
quorum
sensing
(QS).
For
staphylococcal
pathogens
such
as
S.
aureus
,
QS
regulates
expression
of
major
virulence
factors
and
inhibition
has
been
proposed
an
alternative
antibiotics
for
treatment
infections
with
methicillin
resistant
(MRSA).
Here,
we
surveyed
the
interaction
map
between
systems
Staphylococcus
aureus,
epidermidis
lugdunensis
36
currently
known
AIPs
from
22
species.
We
identified
seven
these
ribosomally
synthesized
post-translationally
modified
(RiPPs)
in
this
study
all
synthetic
were
assessed
their
ability
modulate
QS.
The
mapped
interactions
>280
native
pairings
divided
into
human-
animal-associated
staphylococci
showing
substantial
differences
inhibitory
potencies
groups.
In
particular,
bovine-associated
species
simulans
displayed
potential
inhibitors
strains
investigated
therefore
chosen
starting
point
structure–activity
relationship
study.
This
provides
insights
requirements
interference,
yielding
most
potent
reported
date
.
Further,
tested
AIP
anti-virulence
agent
assay
assess
risk
acquired
suppression
effect,
established
set-up
successfully
monitor
agr
deactivation
virulent
MRSA
by
inhibitor.
Finally,
peptide
was
shown
attenuate
skin
infection
caused
mouse
model.
Our
results
reveal
complex
network
provide
further
impetus
development
therapeutic
strategies,
based
on
modulation
target
antibiotic-resistant
pathogens.
TOC
Graphic
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 8, 2025
Atopic
dermatitis
(AD)
is
a
multifactorial,
chronic
relapsing
disease.
Staphylococcus
aureus
the
key
microbial
factor
in
AD,
linked
to
disease
activity.
However,
there
limited
knowledge
of
genomic
prevalence
characteristics
and
phenotypic
features
S.
AD
patients
China.
We
investigated
108
China
globally
publicly
available
genome
sequences
579
AD.
Sequence
type
(ST)
7,
ST15
ST188
were
major
lineages
Genes
esaC,
esxB,
sea
only
detected
ST7,
potentially
contributing
its
exhibited
high
virulence
adhesion,
possibly
due
cna
gene.
Phylogenetic
population
structure
analysis
revealed
that
strains
global
classified
into
15
sequence
clusters
(SCs),
with
SC5,
SC2,
SC7
dominating.
Chinese
was
mainly
distributed
SC7,
SC12.
Comparative
highlighted
genes
including
enterotoxins
(seh,
selk,
selq,
entH),
adhesion
(fnbA,
fnbB,
sdrD,
map,
fib,
narH).
From
perspectives,
we
analyzed
aureus's
epidemic
traits,
phylogeny,
skin.
These
findings
contribute
understanding
aureus-host
interactions
diversity
PLoS ONE,
Год журнала:
2025,
Номер
20(4), С. e0318695 - e0318695
Опубликована: Апрель 7, 2025
Staphylococcus
aureus
(
S.
)
is
a
leading
cause
of
nosocomial
infections,
particularly
among
antibiotic-resistant
strains.
virulence
governed
by
the
accessory
gene
regulator
(Agr)
quorum
sensing
(QS)
system,
which
relies
on
AgrC,
two-component
histidine
kinase,
to
detect
secreted
auto-inducing
peptides
(AIPs).
Emerging
evidence
highlights
potential
inhibiting
interaction
between
AgrC
and
AIPs
as
promising
therapeutic
strategy.
Given
limited
clinic
methods
in
we
hereby
report
novel
method
utilizing
TurboID,
an
engineered
biotin
ligase,
inhibit
Agr
C
via
its
biotinylation.
To
achieve
this
goal,
fusion
protein
named
TurboID-AgrD
1−32
(Agr-ID)
was
designed
include
binding
domain
(AgrID
id="m2">1
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 10, 2024
The
virulence
of
Staphylococcus
aureus,
including
methicillin-resistant
S.
aureus
(MRSA),
depends
on
the
expression
toxins
and
factors
controlled
by
quorum-sensing
(QS)
system,
encoded
accessory
gene
regulator
(agr)
locus.
aim
this
study
was
to
identify
a
phytochemical
that
inhibits
Agr-QS
function
elucidate
its
mechanism.
We
screened
577
compounds
identified
physalin
H,
B,
isophysalin
B--phytochemicals
belonging
physalins
found
in
plants
Solanaceae
family--as
novel
modulators.
Biological
analyses
vitro
protein-DNA
binding
assays
suggested
these
suppress
related
system
inhibiting
key
response
AgrA
agr
promoters,
reducing
hemolytic
downstream
genes
MRSA.
Furthermore,
although
F
suppressed
anti-hemolytic
activity
lower
than
B.
Conversely,
five
isolated
from
same
plant
with
ability
did
not
reduce
bacterial
but
inhibited
DNA
vitro.
A
docking
simulation
revealed
interacts
DNA-binding
site
three
states.
carbonyl
oxygens
at
C-1
C-18
physalins,
which
can
Agr-QS,
were
directed
residues
N201
R198
AgrA,
respectively,
whereas
without
suppression
activity,
oriented
different
directions.
Next,
100-ns
molecular
dynamics
simulations
hydrogen
bond
formed
between
oxygen
C-15
L186
functions
as
an
anchor,
sustaining
interaction
AgrA.
Thus,
results
suggest
B
inhibit
promoters
suppressing
aureus.
Physalins
are
proposed
potential
lead
anti-virulence
strategy
for
MRSA
infections.
