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
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 26, 2025
Recalcitrant
bacterial
infections
can
be
caused
by
various
types
of
dormant
bacteria,
including
persisters
and
viable
but
nonculturable
(VBNC)
cells.
Despite
their
clinical
importance,
we
know
fairly
little
about
dormancy
development
recovery.
Previously,
established
a
correlation
between
protein
aggregation
in
Escherichia
coli.
Here,
present
further
support
for
direct
relationship
both.
Our
experiments
demonstrate
that
aggregates
progressively
sequester
proteins
involved
energy
production,
thereby
likely
causing
ATP
depletion
dormancy.
Furthermore,
structural
features
determine
the
cell's
ability
to
exit
resume
growth.
Proteins
were
shown
first
assemble
liquid-like
condensates
solidify
over
time.
This
liquid-to-solid
phase
transition
impedes
aggregate
dissolution,
preventing
growth
resumption.
data
model
which
structure,
rather
than
cellular
activity,
marks
from
persister
VBNC
state.
are
often
authors
explore
how
composition
structure
affect
this
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Авг. 10, 2021
Abstract
Across
the
tree
of
life,
populations
have
evolved
capacity
to
contend
with
suboptimal
conditions
by
engaging
in
dormancy,
whereby
individuals
enter
a
reversible
state
reduced
metabolic
activity.
The
resulting
seed
banks
are
complex,
storing
information
and
imparting
memory
that
gives
rise
multi-scale
structures
networks
spanning
collections
cells
entire
ecosystems.
We
outline
fundamental
attributes
emergent
phenomena
associated
dormancy
banks,
vision
for
unifying
mathematically
based
framework
can
address
problems
life
sciences,
ranging
from
global
change
cancer
biology.
Frontiers in Microbiology,
Год журнала:
2022,
Номер
12
Опубликована: Фев. 2, 2022
Bacterial
persisters
are
a
sub-population
of
phenotypic
variants
that
tolerate
high
concentrations
antibiotics
within
the
genetically
homogeneous
cells.
They
resume
division
upon
removal
drugs.
persistence
is
one
major
causes
antibiotic
treatment
failure
and
recurrent
infection.
Cell
dormancy,
triggered
by
toxin/antitoxin
pair,
(p)ppGpp,
SOS
response
ATP
levels,
known
to
be
mechanistic
basis
for
persistence.
However,
recent
studies
have
demonstrated
bacteria
with
active
metabolism
can
maintain
lowering
intracellular
concentration
via
an
efflux
pump.
Additionally,
others
our
work
showed
cell
wall
deficient
(CWDB),
including
both
L-form
spheroplasts
produced
β-lactam
antibiotics,
associated
not
dormant
cells
as
their
walls
been
completely
damaged.
In
this
review,
we
discuss
various
types
highlight
contribution
non-walled
on
bacterial
Cell Insight,
Год журнала:
2023,
Номер
2(4), С. 100104 - 100104
Опубликована: Апрель 24, 2023
Over
the
years,
much
attention
has
been
drawn
to
antibiotic
resistance
bacteria,
but
drug
inefficacy
caused
by
a
subgroup
of
special
phenotypic
variants
–
persisters
largely
neglected
in
both
scientific
and
clinical
field.
Interestingly,
this
displayed
their
power
withstanding
sufficient
antibiotics
exposure
mechanism
different
from
resistance.
In
review,
we
summarized
importance
bacterial
persisters,
evolutionary
link
between
resistance,
tolerance,
persistence,
redundant
mechanisms
persister
formation
as
well
methods
studying
cells.
light
our
recent
findings
membrane-less
organelle
aggresome
its
important
roles
regulating
dormancy
depth,
propose
an
alternative
approach
for
anti-persister
therapy.
That
is,
force
into
deeper
state
become
VBNC
(viable
non-culturable)
cell
that
is
incapable
regrowth.
We
hope
provide
latest
insights
on
studies
call
upon
more
research
interest
