The role of hypermutation and collateral sensitivity in antimicrobial resistance diversity of Pseudomonas aeruginosa populations in cystic fibrosis lung infection
mBio,
Год журнала:
2024,
Номер
15(2)
Опубликована: Янв. 3, 2024
Pseudomonas
aeruginosa
is
an
opportunistic
pathogen
which
causes
chronic,
drug-resistant
lung
infections
in
cystic
fibrosis
(CF)
patients.
In
this
study,
we
explore
the
role
of
genomic
diversification
and
evolutionary
trade-offs
antimicrobial
resistance
(AMR)
diversity
within
P.
populations
sourced
from
CF
infections.
We
analyzed
300
clinical
isolates
four
patients
(75
per
patient)
found
that
not
a
consistent
indicator
phenotypic
AMR
diversity.
Remarkably,
some
genetically
less
diverse
showed
comparable
to
those
with
significantly
more
genetic
variation.
also
observed
hypermutator
strains
frequently
exhibited
increased
sensitivity
antimicrobials,
contradicting
expectations
their
treatment
histories.
Investigating
potential
trade-offs,
no
substantial
evidence
collateral
among
aminoglycoside,
beta-lactam,
or
fluoroquinolone
antibiotics,
nor
did
observe
between
growth
conditions
mimicking
sputum.
Our
findings
suggest
(i)
prerequisite
for
diversity,
(ii)
may
develop
under
selection
pressure,
(iii)
prominent
feature
strains,
(iv)
single
antibiotic
does
necessarily
lead
significant
fitness
costs.
These
insights
challenge
prevailing
assumptions
about
evolution
chronic
infections,
emphasizing
complexity
bacterial
adaptation
during
infection.IMPORTANCEUpon
infection
lung,
rapidly
acquires
mutations,
especially
genes
involved
(AMR),
often
resulting
diverse,
treatment-resistant
populations.
However,
population
context
still
poorly
understood.
undergoing
tobramycin
evolved
relative
non-hypermutators
same
population.
This
finding
suggests
only
exert
weak
pressure
on
lung.
further
these
populations,
suggesting
be
robust,
naturally
occurring
phenomenon
microbe.
Язык: Английский
Burkholderia cenocepacia and Pseudomonas aeruginosa in dual-species models: Insights into population distribution, antibiotic susceptibility, and virulence
Virulence,
Год журнала:
2025,
Номер
16(1)
Опубликована: Апрель 24, 2025
Multispecies
biofilms
are
communities
composed
of
different
microorganisms
embedded
in
an
auto-synthesized
polymeric
matrix.
Pseudomonas
aeruginosa
and
Burkholderia
cenocepacia
two
multidrug-resistant
biofilm-forming
opportunistic
pathogens
often
found
the
lungs
people
living
with
cystic
fibrosis.
In
this
context,
planktonic,
static,
dynamic
vivo
models
both
species
were
optimized
work
to
understand
their
population
dynamics,
disposition,
virulence,
antibiotic
susceptibility.
From
coculture
work,
we
determined
that
B.
grows
a
clustered,
aggregative
manner
at
bottom
layers
biofilms,
close
contact
P.
aeruginosa,
tends
occupy
top
layers.
Their
coexistence
increases
virulence-related
gene
expression
early
stages
coinfection
models,
while
there
was
general
downregulation
genes
after
longer
periods
as
they
eventually
reach
non-competitive
stage
during
chronic
infections.
When
evaluating
antimicrobial
susceptibility,
decrease
tolerance
observed
when
co-cultured.
These
findings
shed
light
on
differential
behavior
dual-species
systems,
stressing
relevance
multispecies
studies
clinical
context.
Язык: Английский
Emerging strategies to target virulence in Pseudomonas aeruginosa respiratory infections
Critical Reviews in Microbiology,
Год журнала:
2023,
Номер
unknown, С. 1 - 16
Опубликована: Ноя. 24, 2023
Pseudomonas
aeruginosa
is
an
opportunistic
pathogen
that
responsible
for
infections
in
people
living
with
chronic
respiratory
conditions,
such
as
cystic
fibrosis
(CF)
and
non-CF
bronchiectasis
(NCFB).
Traditionally,
disorders,
P.
infection
has
been
managed
a
combination
of
inhaled
intravenous
antibiotic
therapies.
However,
due
part
to
the
prolonged
use
antibiotics
these
people,
emergence
multi-drug
resistant
strains
growing
concern.
The
development
anti-virulence
therapeutics
may
provide
new
means
treating
lung
whilst
also
combatting
AMR
crisis,
agents
are
presumed
exert
reduced
pressure
drug
resistance
compared
antibiotics.
pipeline
developing
poorly
defined,
it
currently
unclear
whether
vivo
vitro
models
effectively
replicate
complex
pulmonary
environment
sufficiently
enable
testing
therapies
future
clinical
use.
Here,
we
discuss
potential
targets
effectiveness
current
used
study
them.
Focus
given
difficulty
replicating
virulence
gene
expression
patterns
CF
NCFB
under
laboratory
conditions
challenges
this
poses
therapeutic
development.
Язык: Английский
The Role of Hypermutation and Collateral Sensitivity in Antimicrobial Resistance Diversity ofPseudomonas aeruginosaPopulations in Cystic Fibrosis Lung Infection
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 15, 2023
Abstract
Pseudomonas
aeruginosa
is
an
opportunistic
pathogen
which
causes
chronic,
drug-resistant
lung
infections
in
cystic
fibrosis
(CF)
patients.
In
this
study,
we
explore
the
role
of
genomic
diversification
and
evolutionary
trade-offs
antimicrobial
resistance
(AMR)
diversity
within
P.
populations
sourced
from
CF
infections.
We
analyzed
300
clinical
isolates
four
patients
(75
per
patient),
found
that
not
a
consistent
indicator
phenotypic
AMR
diversity.
Remarkably,
some
genetically
less
diverse
showed
comparable
to
those
with
significantly
more
genetic
variation.
also
observed
hypermutator
strains
frequently
exhibited
increased
sensitivity
antimicrobials,
contradicting
expectations
their
treatment
histories.
Investigating
potential
trade-offs,
no
substantial
evidence
collateral
among
aminoglycoside,
beta-lactam,
or
fluoroquinolone
antibiotics,
nor
did
observe
between
growth
conditions
mimicking
sputum.
Our
findings
suggest
(i)
prerequisite
for
diversity;
(ii)
may
develop
under
selection
pressure;
(iii)
prominent
feature
strains,
(iv)
single
antibiotic
does
necessarily
lead
significant
fitness
costs.
These
insights
challenge
prevailing
assumptions
about
evolution
chronic
infections,
emphasizing
complexity
bacterial
adaptation
during
infection.
Importance
Upon
infection
lung,
rapidly
acquires
mutations,
especially
genes
involved
(AMR),
often
resulting
diverse,
treatment-resistant
populations.
However,
population
context
still
poorly
understood.
undergoing
tobramycin
evolved
relative
non-hypermutators
same
population.
This
finding
suggests
only
exert
weak
pressure
on
lung.
further
these
populations,
suggesting
be
robust,
naturally
occurring
phenomenon
microbe.
Preprint
servers:
manuscript
has
been
submitted
as
preprint
bioRxiv
Язык: Английский