Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(8)
Опубликована: Фев. 29, 2024
Staphylococcus
aureus
is
a
leading
cause
of
biofilm-associated
prosthetic
joint
infection
(PJI).
A
primary
contributor
to
chronicity
an
expansion
granulocytic
myeloid-derived
suppressor
cells
(G-MDSCs)
that
are
critical
for
orchestrating
the
anti-inflammatory
biofilm
milieu.
Single-cell
sequencing
and
bioinformatic
metabolic
algorithms
were
used
explore
link
between
G-MDSC
metabolism
S.
PJI
outcome.
Glycolysis
hypoxia
response
through
hypoxia-inducible
factor-1
alpha
(HIF-1a)
significantly
enriched
in
G-MDSCs.
Interfering
with
both
pathways
vivo,
using
2-deoxyglucose
nanopreparation
granulocyte-targeted
HIF-1a
conditional
knockout
mice,
respectively,
attenuated
G-MDSC-mediated
immunosuppression
reduced
bacterial
burden
mouse
model
PJI.
In
addition,
scRNA-seq
analysis
granulocytes
from
patients
also
showed
enrichment
glycolysis
genes.
These
findings
support
importance
glycolysis/HIF-1a
axis
promoting
activity
persistence
during
Microorganisms,
Год журнала:
2025,
Номер
13(1), С. 181 - 181
Опубликована: Янв. 16, 2025
Using
a
murine
osteomyelitis
model,
we
recently
demonstrated
that
Staphylococcus
aureus
sarA
and
sarA/agr
mutants
generated
in
the
USA300
strain
LAC
are
attenuated
to
greater
extent
than
an
isogenic
agr
mutant
this
can
be
attributed
significant
increased
production
of
extracellular
proteases
both
mutants.
Based
on
this,
used
mass-based
proteomics
approach
compare
proteomes
LAC,
its
agr,
sarA,
mutants,
derivatives
all
four
these
strains
unable
produce
aureolysin,
SspA,
SspB,
ScpA,
or
SplA-F.
This
allowed
us
identify
proteins
were
present
reduced
amounts
owing
proteases.
A
total
1039
detected
conditioned
media
(CM)
from
overnight
cultures
protease-mediated
degradation
was
shown
contribute
abundance
224
(21.6%)
CM
Among
specific
previously
implicated
pathogenesis
therapeutic
recalcitrance
S.
osteomyelitis.
demonstrates
ability
limit
protease
plays
key
role
post-translational
remodeling
proteome
degree
correlated
with
virulence
our
it
does
so
irrespective
functional
status
agr.
also
suggests
at
least
some
may
viable
targets
for
prophylactic
intervention.
Proceedings of the National Academy of Sciences,
Год журнала:
2021,
Номер
118(7)
Опубликована: Фев. 11, 2021
Staphylococcus
aureus
causes
invasive
infections
and
easily
acquires
antibiotic
resistance.
Even
antibiotic-susceptible
S.
can
survive
therapy
persist,
requiring
prolonged
treatment
surgical
interventions.
These
so-called
persisters
display
an
arrested-growth
phenotype,
tolerate
high
concentrations,
are
associated
with
chronic
recurrent
infections.
To
characterize
these
persisters,
we
assessed
recovered
directly
from
a
patient
suffering
persistent
infection.
We
show
that
host-mediated
stress,
including
acidic
pH,
abscess
environment,
exposure
promoted
persister
formation
in
vitro
vivo.
Multiomics
analysis
identified
molecular
changes
response
to
acid
stress
leading
overall
virulent
population.
However,
further
of
persister-enriched
population
revealed
major
reprogramming
down-regulation
virulence
cell
division
up-regulation
ribosomal
proteins,
nucleotide-,
amino
acid-metabolic
pathways,
suggesting
their
requirement
fuel
maintain
the
phenotype
highlighting
not
completely
metabolically
inactive.
Additionally,
decreased
aconitase
activity
ATP
levels
accumulation
insoluble
proteins
involved
transcription,
translation,
energy
production
correlated
persistence
aureus,
underpinning
mechanisms
drive
phenotype.
Upon
regrowth,
regained
potential
active
reduction
exhibiting
reversible
state,
crucial
for
targeted
antipersister
combination
using
retinoid
derivatives
antibiotics
significantly
reduced
lag-phase
heterogeneity
murine
infection
model.
Our
results
provide
insights
into
help
explain
why
so
difficult
treat.
Pathogens and Disease,
Год журнала:
2020,
Номер
78(8)
Опубликована: Сен. 18, 2020
ABSTRACT
The
larva
of
the
greater
wax
moth
Galleria
mellonella
is
an
increasingly
popular
model
for
assessing
virulence
bacterial
pathogens
and
effectiveness
antimicrobial
agents.
In
this
review,
we
discuss
details
components
G.
larval
immune
system
that
underpin
its
use
as
alternative
infection
model,
provide
updated
overview
state
art
research
with
models
to
study
virulence,
in
evaluation
efficacy.
Emphasis
given
studies
relevant
human
veterinary
pathogens,
especially
Escherichia
coli
bacteria
ESKAPE
group.
addition,
make
practical
recommendations
rearing
testing,
overcoming
potential
limitations
which
facilitate
intra-
interlaboratory
reproducibility.
Clinical Microbiology Reviews,
Год журнала:
2021,
Номер
34(2)
Опубликована: Фев. 2, 2021
Staphylococcus
aureus
is
a
formidable
bacterial
pathogen
that
responsible
for
infections
in
humans
and
various
species
of
wild,
companion,
agricultural
animals.
The
ability
S.
to
move
between
livestock
due
specific
characteristics
this
bacterium
as
well
modern
practices.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Апрель 7, 2022
Atopic
dermatitis
(AD)
is
a
chronic
inflammatory
skin
disease
characterized
by
barrier
dysfunction,
dysregulated
immune
response,
and
dysbiosis
with
increased
Staphylococcus
aureus
colonization.
Infiltration
of
various
T
helper
cell
subsets
into
lesional
subsequent
cytokine
release
are
hallmark
AD.
Release
cytokines
both
cells
keratinocytes
plays
key
role
in
inflammation
drives
many
AD
features.
This
review
aims
to
discuss
cytokine-mediated
crosstalk
between
pathogenesis
the
potential
impact
virulence
factors
produced
on
these
interactions.
Toxins,
Год журнала:
2022,
Номер
14(2), С. 97 - 97
Опубликована: Янв. 25, 2022
The
present
study
aimed
to
investigate
the
prevalence,
antibiotic
susceptibility
profiles,
and
some
toxin
genes
of
Panton-Valentine
leukocidin
(PVL)-positive
Staphylococcus
aureus
(S.
aureus)
in
unpasteurized
raw
cow's
milk
collected
from
retail
outlets
located
at
Mansoura,
Dakahliya
governorate,
Egypt.
In
that
context,
a
total
700
samples
were
investigated
for
presence
S.
aureus,
which
was
identified
41.1%
(288/700)
samples.
Among
isolates,
113
PVL-positive
subjected
further
analysis.
existence
toxin-related
genes,
including
hemolysin
(hla),
toxic
shock
syndrome
toxin-1
(tst),
enterotoxins
(sea,
seb,
sec,
see,
seg,
sei,
selj).
Genotypic
resistance
strains
performed
detection
blaZ
mecA
genes.
sea,
sec
detected
44.2,
6.2%,
0.9%,
respectively,
while
hla
tst
54.9%
respectively.
successfully
84.9
(96/113)
32.7%
(37/113)
evaluated
displayed
high
level
penicillin,
ampicillin,
trimethoprim-sulfamethoxazole.
Multidrug
(resistant
≥3
antimicrobial
classes)
by
all
methicillin-resistant
(MRSA)
38.2%
methicillin-sensitive
(MSSA)
isolates.
obtained
findings
are
raising
alarm
virulent
MRSA
clones
Egypt,
suggesting
requirement
limiting
use
β-lactam
drugs
food-producing
animals
importance
implementing
strong
hygiene
procedures
dairy
farms
processing
plants.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
25(1), С. 395 - 395
Опубликована: Дек. 28, 2023
Staphylococcus
aureus
stands
as
one
of
the
most
pervasive
pathogens
given
its
morbidity
and
mortality
worldwide
due
to
roles
an
infectious
agent
that
causes
a
wide
variety
diseases
ranging
from
moderately
severe
skin
infections
fatal
pneumonia
sepsis.
S.
produces
exotoxins
serve
important
virulence
factors
in
aureus-related
food
poisoning
both
humans
animals.
For
example,
staphylococcal
enterotoxins
(SEs)
produced
by
induce
foodborne
poisoning;
toxic
shock
syndrome
toxin-1
(TSST-1),
typical
superantigen,
induces
syndrome;
hemolysins
cell
damage
erythrocytes
leukocytes;
exfoliative
toxin
scalded
syndrome.
Recently,
Panton–Valentine
leucocidin,
cytotoxin
community-associated
methicillin-resistant
(CA-MRSA),
has
been
reported,
new
types
SEs
enterotoxin-like
toxins
(SEls)
were
discovered
reported
successively.
This
review
addresses
progress
novel
insights
into
molecular
structure,
biological
activities,
pathogenicity
classic
newly
identified
aureus.
The Lancet Microbe,
Год журнала:
2023,
Номер
5(1), С. e52 - e61
Опубликована: Дек. 1, 2023
Metagenomic
next-generation
sequencing
(mNGS)
allows
untargeted
identification
of
a
broad
range
pathogens,
including
rare
or
novel
microorganisms.
Despite
the
recognition
mNGS
as
valuable
diagnostic
tool
for
infections,
most
relevant
indications
this
innovative
strategy
remain
poorly
defined.
We
aimed
to
assess
determinants
positivity
and
clinical
utility
mNGS.