Microbiology Spectrum,
Journal Year:
2023,
Volume and Issue:
11(3)
Published: May 4, 2023
Clinicians
are
increasingly
confronted
with
the
limitations
of
antibiotics
to
clear
bacterial
infections
in
patients.
It
has
long
been
assumed
that
only
antibiotic
resistance
plays
a
pivotal
role
this
phenomenon.
Indeed,
worldwide
emergence
is
considered
one
major
health
threats
21st
century.
However,
presence
persister
cells
also
significant
influence
on
treatment
outcomes.
These
antibiotic-tolerant
present
every
population
and
result
phenotypic
switching
normal,
antibiotic-sensitive
cells.
Persister
complicate
current
therapies
contribute
development
resistance.
In
past,
extensive
research
performed
investigate
persistence
laboratory
settings;
however,
tolerance
under
conditions
mimic
clinical
setting
remain
poorly
understood.
study,
we
optimized
mouse
model
for
lung
opportunistic
pathogen
Pseudomonas
aeruginosa.
model,
mice
intratracheally
infected
P.
aeruginosa
embedded
seaweed
alginate
beads
subsequently
treated
tobramycin
via
nasal
droplets.
A
diverse
panel
18
strains
originating
from
environmental,
human,
animal
sources
was
selected
assess
survival
model.
Survival
levels
were
positively
correlated
determined
time-kill
assays,
common
method
study
laboratory.
We
showed
comparable
thus
classical
assays
indicative
setting.
The
enables
us
test
potential
antipersister
relevant
settings.
IMPORTANCE
importance
targeting
becoming
more
evident,
as
these
underlie
relapsing
development.
Here,
studied
clinically
pathogen,
six
ESKAPE
pathogens
(Enterococcus
faecium,
Staphylococcus
aureus,
Klebsiella
pneumoniae,
Acinetobacter
baumannii,
aeruginosa,
Enterobacter
spp.),
which
threats.
mostly
known
cause
chronic
cystic
fibrosis
mimicked
conditions.
shown
natural
isolates
measured
vitro.
results
not
validate
use
our
techniques
but
open
opportunities
new
mechanisms
or
evaluate
strategies
vivo.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 2, 2024
Abstract
Bacteriophages
are
ubiquitous
viral
predators
that
have
primarily
been
studied
using
fast-growing
laboratory
cultures
of
their
bacterial
hosts.
However,
microbial
life
in
nature
is
mostly
a
slow-
or
non-growing,
dormant
state.
Here,
we
show
diverse
phages
can
infect
deep-dormant
bacteria
and
suspend
replication
until
the
host
resuscitates
(“hibernation”).
newly
isolated
Pseudomonas
aeruginosa
phage,
named
Paride,
directly
replicate
induce
lysis
While
non-growing
notoriously
tolerant
to
antibiotic
drugs,
combination
with
Paride
enables
carbapenem
meropenem
eradicate
vitro
reduce
resilient
infection
tissue
cage
implant
mice.
Our
work
might
inspire
new
treatments
for
persistent
infections
and,
more
broadly,
highlights
two
strategies
(hibernation
direct
replication)
will
guide
future
studies
on
phage-host
interactions.
npj Biofilms and Microbiomes,
Journal Year:
2022,
Volume and Issue:
8(1)
Published: Oct. 18, 2022
Abstract
Experimental
evolution
experiments
in
which
bacterial
populations
are
repeatedly
exposed
to
an
antimicrobial
treatment,
and
examination
of
the
genotype
phenotype
resulting
evolved
bacteria,
can
help
shed
light
on
mechanisms
behind
reduced
susceptibility.
In
this
review
we
present
overview
why
it
is
important
include
biofilms
experimental
evolution,
approaches
available
study
what
has
taught
us
about
tolerance
resistance
biofilms.
Finally,
emerging
consensus
view
biofilm
susceptibility
supported
by
data
obtained
during
studies.
microLife,
Journal Year:
2023,
Volume and Issue:
4
Published: Jan. 1, 2023
The
stringent
response
and
its
signalling
nucleotides,
pppGpp
ppGpp,
have
been
the
subject
of
intense
research
since
discovery
(p)ppGpp
in
1969.
Recent
studies
revealed
that
downstream
events
follow
accumulation
vary
among
species.
Consequently,
as
initially
characterized
Antibiotics,
Journal Year:
2023,
Volume and Issue:
12(6), P. 1044 - 1044
Published: June 12, 2023
Antibiotic
therapy
failure
is
often
caused
by
the
presence
of
persister
cells,
which
are
metabolically-dormant
bacteria
capable
surviving
exposure
to
antimicrobials.
Under
favorable
conditions,
persisters
can
resume
growth
leading
recurrent
infections.
Moreover,
several
studies
have
indicated
that
may
promote
evolution
antimicrobial
resistance
and
facilitate
selection
specific
resistant
mutants;
therefore,
in
light
increasing
numbers
multidrug-resistant
infections
worldwide,
developing
efficient
strategies
against
dormant
cells
paramount
importance.
In
this
review,
we
present
discuss
efficacy
various
agents
whose
activity
independent
metabolic
status
as
they
target
cell
envelope
structures.
Since
biofilm-environment
for
formation
subpopulations,
anti-persister
should
also
include
destroy
biofilm
matrix
or
inhibit
development.
This
article
reviews
examples
selected
wall
hydrolases,
polysaccharide
depolymerases
peptides.
Their
combination
with
standard
antibiotics
seems
be
most
promising
approach
combating
persistent
PLoS neglected tropical diseases,
Journal Year:
2022,
Volume and Issue:
16(7), P. e0010635 - e0010635
Published: July 26, 2022
Background
Human
brucellosis
caused
by
the
facultative
intracellular
pathogen
Brucella
spp.
is
an
endemic
bacterial
zoonosis
manifesting
as
acute
or
chronic
infections
with
high
morbidity.
Treatment
typically
involves
a
combination
therapy
of
two
antibiotics
for
several
weeks
to
months,
but
despite
this
harsh
treatment
relapses
occur
at
rate
5–15%.
Although
poor
compliance
and
reinfection
may
account
fraction
observed
relapse
cases,
it
apparent
that
properties
infectious
agent
itself
play
decisive
role
in
phenomenon.
Methodology/Principal
findings
We
used
B
.
abortus
carrying
dual
reporter
macrophage
infection
model
gain
better
understanding
efficacy
recommended
therapies
cellulo
For
we
automated
fluorescent
microscopy
prime
read-out
developed
specific
CellProfiler
pipelines
score
infected
macrophages
population
single
cell
level.
Combining
constitutive
induced
reporters
classical
CFU
determination,
quantified
protective
nature
lifestyle
various
ability
persist
antibiotic
treatments.
Conclusion/Significance
demonstrate
concentrations
fails
fully
prevent
growth
persistence
,
which
be
explained
niche(s).
Moreover,
show
presence
bona
fide
persisters
upon
treatment,
are
metabolically
active
retain
full
potential,
therefore
constituting
plausible
reservoir
relapse.
In
conclusion,
our
results
highlight
need
extend
spectrum
models
test
new
antimicrobial
reflect
vivo
environment,
develop
therapeutic
approaches
targeting
persister
subpopulation.