Persisters
represent
a
small
subpopulation
of
cells
that
are
tolerant
killing
by
antibiotics
and
implicated
in
the
recalcitrance
chronic
infections
to
antibiotic
therapy.
One
general
theme
has
emerged
regarding
persisters
formed
different
bacterial
species,
namely,
state
relative
dormancy
characterized
diminished
activity
targets.
Within
this
framework,
number
studies
have
linked
persister
formation
stochastic
decreases
energy-generating
components,
leading
low
ATP
target
activity.
In
study,
we
screen
knockouts
main
global
regulators
Escherichia
coli
for
their
effect
on
persisters.
A
knockout
integration
host
factor
(IHF)
had
elevated
level
This
was
accompanied
an
overexpression
isocitrate
dehydrogenase
(Icd)
downregulation
lyase
(AceA),
two
genes
located
at
bifurcation
between
tricarboxylic
acid
(TCA)
cycle
glyoxylate
bypass.
Using
translational
ihfA-mVenus
fusion,
sort
out
rare
bright
cells,
is
enriched
Our
results
suggest
noise
expression
ihf
produces
with
Icd/high
AceA,
diverting
substrates
into
bypass,
which
ATP,
antibiotic-tolerant
We
further
examine
simple
model,
lac
operon,
show
lacI
repressor
increases
operon
formation.
quenching
serves
as
approach
determine
nature
variety
species
conditions.
IMPORTANCE
phenotypic
variants
survive
exposure
through
temporary
dormancy.
Mutants
increased
levels
been
identified
clinical
isolates,
evidence
suggests
these
contribute
treatment
failure.
Understanding
underlying
mechanism
tolerance
important
developing
therapeutic
approaches
treat
infections.
regulator,
IHF,
plays
role
find
IHF
contributes
formation,
likely
regulating
switch
TCA
efficiently
energy
extend
study
model
when
grown
lactose
sole
carbon
source,
its
influences
determines
quenched
providing
test
involvement
gene
The
annual
incidence
of
Lyme
disease,
caused
by
tick-transmitted
Borreliella
burgdorferi
,
is
estimated
to
be
at
least
476,000
cases
in
the
United
States
and
many
more
worldwide.
Ten
20%
antimicrobial-treated
disease
patients
display
posttreatment
syndrome
(PTLDS),
a
clinical
complication
whose
etiology
pathogenesis
remain
uncertain.
Science Signaling,
Год журнала:
2023,
Номер
16(766)
Опубликована: Янв. 3, 2023
Staphylococcus
aureus
can
cause
infections
that
are
often
chronic
and
difficult
to
treat,
even
when
the
bacteria
not
antibiotic
resistant
because
most
antibiotics
act
only
on
metabolically
active
cells.
Subpopulations
of
persister
cells
quiescent,
a
state
associated
with
delayed
growth,
reduced
protein
synthesis,
increased
tolerance
antibiotics.
Serine-threonine
kinases
phosphatases
similar
those
found
in
eukaryotes
fine-tune
essential
bacterial
cellular
processes,
such
as
metabolism
stress
signaling.
We
acid
stress-mimicking
conditions
S.
experiences
host
tissues
globally
altered
serine
threonine
phosphoproteome,
phosphorylation
activation
loop
serine-threonine
kinase
B
(PknB).
The
deletion
stp,
which
encodes
annotated
functional
phosphatase
aureus,
growth
delay
phenotypic
heterogeneity
under
different
challenges,
including
acidic
conditions,
intracellular
milieu
human
cells,
abscesses
mice.
This
was
translation
ATP
concentrations
tolerance.
Using
phosphopeptide
enrichment
mass
spectrometry-based
proteomics,
we
identified
targets
may
regulate
metabolism.
Together,
our
findings
highlight
importance
phosphoregulation
mediating
quiescence
suggest
targeting
PknB
or
Stp
might
offer
future
therapeutic
strategy
prevent
formation
during
infections.
Persisters
represent
a
small
subpopulation
of
cells
that
are
tolerant
killing
by
antibiotics
and
implicated
in
the
recalcitrance
chronic
infections
to
antibiotic
therapy.
One
general
theme
has
emerged
regarding
persisters
formed
different
bacterial
species,
namely,
state
relative
dormancy
characterized
diminished
activity
targets.
Within
this
framework,
number
studies
have
linked
persister
formation
stochastic
decreases
energy-generating
components,
leading
low
ATP
target
activity.
In
study,
we
screen
knockouts
main
global
regulators
Escherichia
coli
for
their
effect
on
persisters.
A
knockout
integration
host
factor
(IHF)
had
elevated
level
This
was
accompanied
an
overexpression
isocitrate
dehydrogenase
(Icd)
downregulation
lyase
(AceA),
two
genes
located
at
bifurcation
between
tricarboxylic
acid
(TCA)
cycle
glyoxylate
bypass.
Using
translational
ihfA-mVenus
fusion,
sort
out
rare
bright
cells,
is
enriched
Our
results
suggest
noise
expression
ihf
produces
with
Icd/high
AceA,
diverting
substrates
into
bypass,
which
ATP,
antibiotic-tolerant
We
further
examine
simple
model,
lac
operon,
show
lacI
repressor
increases
operon
formation.
quenching
serves
as
approach
determine
nature
variety
species
conditions.
IMPORTANCE
phenotypic
variants
survive
exposure
through
temporary
dormancy.
Mutants
increased
levels
been
identified
clinical
isolates,
evidence
suggests
these
contribute
treatment
failure.
Understanding
underlying
mechanism
tolerance
important
developing
therapeutic
approaches
treat
infections.
regulator,
IHF,
plays
role
find
IHF
contributes
formation,
likely
regulating
switch
TCA
efficiently
energy
extend
study
model
when
grown
lactose
sole
carbon
source,
its
influences
determines
quenched
providing
test
involvement
gene
