ABSTRACT
Chronic
polymicrobial
infections
involving
Pseudomonas
aeruginosa
and
Staphylococcus
aureus
are
prevalent,
difficult
to
eradicate,
associated
with
poor
health
outcomes.
Therefore,
understanding
interactions
between
these
pathogens
is
important
inform
improved
treatment
development.
We
previously
demonstrated
that
P.
attracted
S.
using
type
IV
pili
(TFP)-mediated
chemotaxis,
but
the
impact
of
attraction
on
growth
physiology
remained
unknown.
Using
live
single-cell
confocal
imaging
visualize
microcolony
structure,
spatial
organization,
survival
during
coculture,
we
found
interspecies
chemotaxis
provides
a
competitive
advantage
by
promoting
invasion
into
disruption
microcolonies.
This
behavior
renders
susceptible
antimicrobials.
Conversely,
in
absence
TFP
motility,
cells
exhibit
reduced
colonies.
Instead,
builds
cellular
barrier
adjacent
secretes
diffusible,
bacteriostatic
antimicrobials
like
2-heptyl-4-hydroxyquinoline-
N
-oxide
(HQNO)
Reduced
leads
formation
denser
thicker
colonies
increased
HQNO-mediated
lactic
acid
fermentation,
physiological
change
could
complicate
strategies.
Finally,
show
motility
modifications
structure
enhance
competition
against
.
Overall,
studies
expand
our
how
TFP-mediated
facilitates
interactions,
highlighting
importance
positioning
mixed-species
communities.
IMPORTANCE
The
nature
many
chronic
makes
their
eradication
challenging.
Particularly,
coisolation
from
airways
people
cystic
fibrosis
wound
common
severe
clinical
complex
interplay
not
fully
understood,
need
for
continued
research
improve
management
infections.
Our
study
unveils
,
invades
neighboring
colonies,
anti-staphylococcal
factors
interior
colony.
Upon
inhibition
thus
invasion,
colony
architecture
changes
dramatically,
whereby
protected
antagonism
responds
through
alterations
may
further
hamper
treatment.
These
reinforce
accumulating
evidence
structuring
can
dictate
community
resilience
reveal
critical
drivers
competition.
iScience,
Journal Year:
2023,
Volume and Issue:
26(9), P. 107557 - 107557
Published: Aug. 7, 2023
Acinetobacter
baumannii
causes
a
wide
range
of
infections,
including
wound
infections.
Multidrug-resistant
A.
is
major
healthcare
concern
and
the
development
novel
treatments
against
these
infections
needed.
Fosmidomycin
repurposed
antimalarial
drug
targeting
non-mevalonate
pathway,
several
derivatives
show
activity
toward
baumannii.
We
evaluated
antimicrobial
CC366,
fosmidomycin
prodrug,
collection
strains,
using
various
in
vitro
vivo
models;
emphasis
was
placed
on
evaluation
its
anti-biofilm
activity.
also
developed
3D-printed
dressing
containing
melt
electrowriting
technology.
Minimal
inhibitory
concentrations
CC366
ranged
from
1
to
64
μg/mL,
showed
good
biofilm
moderate
eradicating
vitro.
successfully
eluted
dressing,
dressings
prevented
formation
baumannnii
biofilms
reduced
infection
an
mouse
model.
Microbiology Spectrum,
Journal Year:
2023,
Volume and Issue:
12(1)
Published: Dec. 11, 2023
ABSTRACT
The
ubiquitous
opportunistic
pathogen
Pseudomonas
aeruginosa
is
highly
adaptive
and
refractory
to
several
different
classes
of
antibiotics.
However,
we
found
in
this
study
that
stationary-phase
P.
cultures
exhibit
greater
sensitivity
the
fluoroquinolone
Levofloxacin
(Levo)
than
other
bactericidal
antibiotics,
including
an
aminoglycoside
(Tobramycin)
β-lactam
(Aztreonam).
To
understand
basis
sensitivity,
conducted
time-lapse
fluorescence
microscopy
experiments
cells
during
Levo
treatment.
We
discovered
die
rapidly
treatment
undergo
heterogeneous
morphological
changes,
explosive
lysis,
filamentation,
gradual
loss
membrane
integrity
as
evidenced
by
propidium
iodide
uptake.
These
morphologies
are
reminiscent
how
model
organism
Escherichia
coli
appears
when
recovering
from
treatment,
a
period
activation
DNA
damage-induced
SOS
response
crucial.
Accordingly,
monitored
survival
Δ
recA
mutants
not
involved
like
it
for
E.
.
hypothesized
may
be
due
maintaining
active
metabolism
stationary
phase.
determined
transcribe,
maintain
reductase
activity,
accumulate
reactive
metabolic
species
which
contribute
Levo-mediated
death.
By
elucidating
sustain
activity
phase,
can
design
strategies
sensitize
these
persistent
subpopulations
efficacy
clinically
important
antibiotic.
IMPORTANCE
bacterial
responsible
variety
chronic
human
infections.
Even
absence
identifiable
resistance
mutations,
tolerate
lethal
antibiotic
doses
through
phenotypic
biofilm
formation
quiescence.
In
study,
maintains
phase
compared
organism,
,
has
traditionally
been
used
tolerance.
demonstrate
hallmarks
tolerance
conserved
timing
cell
death
necessity
damage
survival.
heightened
fluoroquinolones
attributed
maintained
transcriptional
activity.
Our
data
suggest
perturbations
suppress
transcription
respiration
actually
protect
against
class
Journal of the American Society for Mass Spectrometry,
Journal Year:
2023,
Volume and Issue:
34(9), P. 1847 - 1857
Published: June 8, 2023
Concerns
about
ion
suppression,
spectral
contamination,
or
interference
have
led
to
avoidance
of
polymers
in
mass
spectrometry
(MS)-based
metabolomics.
This
avoidance,
however,
has
left
many
biochemical
fields
underexplored,
including
wounds,
which
are
often
treated
with
adhesive
bandages.
Here,
we
found
that
despite
previous
concerns,
the
addition
an
bandage
can
still
result
biologically
informative
MS
data.
Initially,
a
test
LC-MS
analysis
was
performed
on
mixture
known
chemical
standards
and
polymer
extract.
Results
demonstrated
successful
removal
polymer-associated
features
through
data
processing
step.
Furthermore,
presence
did
not
interfere
metabolite
annotation.
method
then
implemented
context
murine
surgical
wound
infections
covered
inoculated
ABSTRACT
Chronic
polymicrobial
infections
involving
Pseudomonas
aeruginosa
and
Staphylococcus
aureus
are
prevalent,
difficult
to
eradicate,
associated
with
poor
health
outcomes.
Therefore,
understanding
interactions
between
these
pathogens
is
important
inform
improved
treatment
development.
We
previously
demonstrated
that
P.
attracted
S.
using
type
IV
pili
(TFP)-mediated
chemotaxis,
but
the
impact
of
attraction
on
growth
physiology
remained
unknown.
Using
live
single-cell
confocal
imaging
visualize
microcolony
structure,
spatial
organization,
survival
during
coculture,
we
found
interspecies
chemotaxis
provides
a
competitive
advantage
by
promoting
invasion
into
disruption
microcolonies.
This
behavior
renders
susceptible
antimicrobials.
Conversely,
in
absence
TFP
motility,
cells
exhibit
reduced
colonies.
Instead,
builds
cellular
barrier
adjacent
secretes
diffusible,
bacteriostatic
antimicrobials
like
2-heptyl-4-hydroxyquinoline-
N
-oxide
(HQNO)
Reduced
leads
formation
denser
thicker
colonies
increased
HQNO-mediated
lactic
acid
fermentation,
physiological
change
could
complicate
strategies.
Finally,
show
motility
modifications
structure
enhance
competition
against
.
Overall,
studies
expand
our
how
TFP-mediated
facilitates
interactions,
highlighting
importance
positioning
mixed-species
communities.
IMPORTANCE
The
nature
many
chronic
makes
their
eradication
challenging.
Particularly,
coisolation
from
airways
people
cystic
fibrosis
wound
common
severe
clinical
complex
interplay
not
fully
understood,
need
for
continued
research
improve
management
infections.
Our
study
unveils
,
invades
neighboring
colonies,
anti-staphylococcal
factors
interior
colony.
Upon
inhibition
thus
invasion,
colony
architecture
changes
dramatically,
whereby
protected
antagonism
responds
through
alterations
may
further
hamper
treatment.
These
reinforce
accumulating
evidence
structuring
can
dictate
community
resilience
reveal
critical
drivers
competition.