bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 25, 2023
Abstract
Background
Phosphorylation
of
proteins
at
serine,
threonine,
and
tyrosine
residues
plays
an
important
role
in
physiological
processes
bacteria
such
as
cell
cycle,
metabolism,
virulence,
dormancy,
sporulation,
stationary
phase
functions.
Streptococcus
pyogenes
possesses
a
single
known
transmembrane
serine/threonine
kinase
belonging
to
the
class
penicillin-binding
protein
serine/threonine-associated
(PASTA)
kinases.
To
gain
initial
insights
into
targets
dynamics
phosphorylation
S.
serotype
M49
strain
591,
we
performed
proteomics
phosphoproteomics
workflow
using
cultures
from
different
growth
conditions,
starvation.
Results
The
quantitative
analysis
dynamic
phosphorylation,
which
included
subset
463
out
815
identified
sites,
revealed
two
main
types
events,
distinguished
by
they
predominantly
occur
their
preference
for
either
threonine
or
serine.
A
small
group
events
occurred
almost
exclusively
related
cycle
was
enhanced
growing
cells.
Many
these
sites
are
highly
conserved
PASTA
kinases
streptococci.
majority
during
starvation,
preferentially
serine
residues.
These
phosphorylations
may
be
regulatory
persister
formation,
but
function
responsible
formation
need
elucidated
further
analyses.
Moreover,
our
data
indicate
that
vast
can
phosphorylated,
identification
phosphopeptides
depends
on
sensitivity
proteomic
methods
used.
Conclusions
kinase-dependent
regulation
found
,
account
only
part
all
events.
Most
take
place
This
phenomenon
has
also
been
described
some
other
therefore
general
feature
bacterial
phosphorylation.
Infection and Drug Resistance,
Год журнала:
2023,
Номер
Volume 16, С. 3271 - 3292
Опубликована: Май 1, 2023
Staphylococcus
aureus
is
a
common
human
pathogen
with
variety
of
virulence
factors,
which
can
cause
multiple
infectious
diseases.
In
recent
decades,
due
to
the
constant
evolution
and
abuse
antibiotics,
was
becoming
more
resistant,
infection
rate
MRSA
remained
high,
clinical
treatment
became
difficult.
The
genetic
diversity
mainly
represented
by
continuous
emergence
epidemic
strains,
resulting
in
changes
clones.
Different
classes
resulted
different
epidemics
resistance
characteristics,
could
affect
symptoms
treatments.
had
also
spread
from
traditional
hospitals
community
livestock
environments,
new
clones
established
relationship
between
animals
humans,
promoting
further
MRSA.
Since
mechanism
very
complex,
it
important
clarify
these
mechanisms
at
molecular
level
for
We
firstly
described
SCCmec
elements,
discussed
types
SCCmec,
its
drug
expression
regulations.
Then,
we
how
vanA
operon
makes
resistant
vancomycin
regulation.
Finally,
brief
introduction
given
biofilms
efflux
pump
systems.
Analyzing
help
study
anti-infective
drugs
alleviate
At
end
review,
summarized
strategies
infection,
including
anti-biofilm
agents
inhibitors.
To
sum
up,
here
reviewed
characteristics
aureus,
classifications,
(SCCmec
element,
operon,
biofilm
active
system)
novel
therapy
strategies,
so
as
provide
theoretical
basis
infection.
Microorganisms,
Год журнала:
2024,
Номер
12(3), С. 621 - 621
Опубликована: Март 20, 2024
Phosphorylation
of
proteins
at
serine,
threonine,
and
tyrosine
residues
plays
an
important
role
in
physiological
processes
bacteria,
such
as
cell
cycle,
metabolism,
virulence,
dormancy,
stationary
phase
functions.
Little
is
known
about
the
targets
dynamics
protein
phosphorylation
Streptococcus
pyogenes,
which
possesses
a
single
transmembrane
serine/threonine
kinase
belonging
to
class
PASTA
kinases.
A
proteomics
phosphoproteomics
workflow
was
performed
with
S.
pyogenes
serotype
M49
under
different
growth
conditions,
phase,
starvation.
The
quantitative
analysis
dynamic
phosphorylation,
included
subset
463
out
815
identified
sites,
revealed
two
main
types
events.
small
group
events
occurred
almost
exclusively
threonine
related
cycle
enhanced
growing
cells.
majority
during
or
starvation,
preferentially
serine
residues.
kinase-dependent
regulation
found
bacteria
are
conserved
pyogenes.
Increased
has
also
been
described
for
some
other
could
therefore
be
general
feature
physiology
whose
functions
kinases
involved
need
elucidated
further
analyses.
EBioMedicine,
Год журнала:
2025,
Номер
114, С. 105658 - 105658
Опубликована: Апрель 1, 2025
Staphylococcus
aureus
and
its
drug-resistant
mutants
are
mentioned
among
the
WHO's
high-priority
list
of
pathogens.
Antibiotics
like
fluoroquinolones
cephalosporins
used
to
treat
multidrug-resistant
S.
infections.
However,
a
higher
expression
efflux
pumps
(NorA,
NorB,
AbcA)
induces
multidrug
resistance.
The
master
regulator,
MgrA,
regulates
most
these
in
aureus.
phosphorylation
status
MgrA
is
determined
by
cellular
PknB/RsbU
ratio,
where
PknB,
serine-threonine
kinase,
RsbU,
phosphatase,
critical
for
functioning.
An
FDA-approved
drug
library
was
screened
using
an
EtBr-accumulation
assay
identify
pump
inhibitors
(EPIs).
synergy
EPIs
with
antibiotics
studied
vitro
vivo
murine
skin
infection
model
female
BALB/c
mice.
effect
on
mgrA,
norB,
pknB,
rsbU
gene
expression,
interaction
effects
were
studied.
We
identified
Montelukast
as
effective
EPI,
which
showed
moxifloxacin,
substrate
NorB
pump,
both
model.
Further,
decreased
norB
increased
pknB/rsbU
ratio.
Our
results
demonstrated
that
strongly
interacted
facilitated
phosphorylation,
enhanced
affinity
promoter.
study
repressed
promoted
suppress
activity,
leading
restoration
antibiotic
susceptibility
supported
SERB-DST,
India
(CRG/2021/005069),
BRIC-ILS
core.
Current Opinion in Microbiology,
Год журнала:
2025,
Номер
85, С. 102611 - 102611
Опубликована: Апрель 28, 2025
Bacteria
display
diverse
strategies
for
cell
division,
exemplified
by
the
multicellular
life
cycle
of
Streptomyces,
a
genus
within
Actinomycetota
phylum.
Filamentous
growing
Streptomyces
utilise
two
distinct
division
modes:
during
vegetative
growth,
nonconstricting
cross-walls
divide
mycelial
network
into
long
multinucleate
compartments,
while
reproductive
sporulation
septation
results
in
'multiple
event'
that
produces
dozens
unigenomic
spores
can
separate
and
disperse
environment.
The
cellular
mechanisms
governing
these
types
are
inherently
complex
present
specific
biological
challenges
involve
core
proteins
several
genus-specific
factors.
This
review
highlights
recent
advances
open
questions
our
understanding
biology,
with
focus
on
key
components
interplay
chromosome
machinery,
enabling
organisms
to
grow
as
filaments
form
unicellular
spores.
PLoS ONE,
Год журнала:
2025,
Номер
20(5), С. e0322880 - e0322880
Опубликована: Май 19, 2025
Serine/threonine
kinases
(STKs)
and
serine/threonine
phosphatases
(STPs)
are
widely
present
across
various
organisms
play
crucial
roles
in
regulating
cellular
processes
such
as
growth,
proliferation,
signal
transduction,
other
physiological
functions.
Recent
research
has
increasingly
focused
on
the
regulation
of
STKs
STPs
bacteria.
have
been
well
studied,
identified
characterized
a
variety
bacterial
species.
However,
role
bacteria
remains
less
understood,
number
proteins
is
limited.
It
found
that
most
were
Mg
2+
/Mn
dependent
2C
protein
(PP2Cs),
but
evolutionary
relationship
taxonomic
distribution
PP2C
still
not
fully
elucidated.
In
this
study,
we
utilized
phosphatase
sequences
from
InterPro
database
to
perform
phylogenetic
analysis,
categorizing
family
into
five
groups.
Based
classification,
examined
relationships,
species
distribution,
sequence
structural
variations,
domain
characteristics
phosphatases.
Our
analysis
uncovered
evidence
common
origin
for
These
findings
advance
understanding
phosphatases,
offering
valuable
insights
future
functional
studies
aiding
design
targeted
therapeutics
pathogenic
ACS Infectious Diseases,
Год журнала:
2023,
Номер
10(1), С. 232 - 250
Опубликована: Дек. 28, 2023
Methicillin-resistant
Staphylococcus
aureus
(MRSA)
has
evolved
to
become
resistant
multiple
classes
of
antibiotics.
New
antibiotics
are
costly
develop
and
deploy,
they
have
a
limited
effective
lifespan.
Antibiotic
adjuvants
molecules
that
potentiate
existing
through
nontoxic
mechanisms.
We
previously
reported
loratadine,
the
active
ingredient
in
Claritin,
potentiates
cell-wall
vitro
disrupts
biofilm
formation
hypothesized
inhibition
master
regulatory
kinase
Stk1.
Loratadine
oxacillin
combined
repressed
expression
key
antibiotic
resistance
genes
bla
mec
operons.
additional
involved
resistance,
formation,
other
cellular
pathways
would
be
modulated
when
looking
transcriptome-wide.
To
test
this,
we
used
RNA-seq
quantify
transcript
levels
found
significant
effects
gene
expression,
including
controlling
virulence,
metabolism,
transcription
(core
RNA
polymerase
subunits
sigma
factors),
translation
(a
plethora
encoding
ribosomal
proteins
elongation
factor
Tu).
further
demonstrated
impacts
these
transcriptional
by
investigating
loratadine
treatment
on
intracellular
ATP
levels,
persister
morphology.
minimized
enhanced
survival
infected
Caenorhabditis
elegans.
These
pleiotropic
their
outcomes
MRSA
virulence
phenotypes
position
as
an
attractive
anti-infective
against
MRSA.
Molecular Microbiology,
Год журнала:
2024,
Номер
122(2), С. 152 - 164
Опубликована: Янв. 3, 2024
Bacteria
possess
diverse
classes
of
signaling
systems
that
they
use
to
sense
and
respond
their
environments
execute
properly
timed
developmental
transitions.
One
widespread
evolutionarily
ancient
class
are
the
Hanks-type
Ser/Thr
kinases,
also
sometimes
termed
"eukaryotic-like"
due
homology
with
eukaryotic
kinases.
In
bacterial
species,
these
function
as
critical
regulators
general
cellular
processes
such
metabolism,
growth
division,
transitions
sporulation,
biofilm
formation,
virulence,
well
antibiotic
tolerance.
This
multifaceted
regulation
is
ability
a
single
kinase
post-translationally
modify
activity
multiple
proteins,
resulting
in
coordinated
pathways.
However,
part
deep
integration
physiology,
date,
we
have
relatively
limited
understanding
timing,
regulatory
hierarchy,
complete
list
targets
given
kinase,
potential
overlap
between
often
kinases
present
organism.
this
review,
discuss
experimental
methods
curated
datasets
aimed
at
elucidating
pathways
approaches
for
using
develop
computational
models
quantitative
predictions
target
motifs.
We
emphasize
novel
opportunities
collecting
data
suitable
creation
new
predictive
applicable
species.