Molecular Microbiology,
Journal Year:
2022,
Volume and Issue:
117(5), P. 1275 - 1290
Published: April 18, 2022
F
plasmids
circulate
widely
among
the
Enterobacteriaceae
through
encoded
type
IV
secretion
systems
(T4SSF
s).
Assembly
of
T4SSF
s
and
associated
pili
requires
10
VirB/VirD4-like
Tra
subunits
eight
or
more
F-specific
subunits.
Recently,
we
presented
evidence
using
in
situ
cryoelectron
tomography
(cryoET)
that
undergo
structural
transitions
when
activated
for
pilus
production,
assembled
are
deposited
onto
alternative
basal
platforms
at
cell
surface.
Here,
deleted
conserved
genes
from
MOBF12C
plasmid
pED208
quantitated
effects
on
transfer,
production
by
fluorescence
microscopy,
elaboration
structures
cryoET.
Mutant
phenotypes
supported
assignment
into
three
functional
Classes:
(i)
TraF,
TraH,
TraW
required
all
-associated
activities,
(ii)
TraU,
TraN,
TrbC
nonessential
but
contribute
significantly
to
distinct
functions,
(iii)
TrbB
is
essential
not
transfer.
Equivalent
mutations
a
phylogenetically
distantly
related
MOB12A
conferred
similar
generally
these
Class
assignments.
We
present
new
structure-driven
model
which
steps
assembly
activation
regulate
DNA
transfer
dynamics
deposition
platforms.
Microbial Biotechnology,
Journal Year:
2025,
Volume and Issue:
18(1)
Published: Jan. 1, 2025
The
increasing
threat
of
antibiotic
resistance
underscores
the
urgent
need
for
innovative
strategies
to
combat
infectious
diseases,
including
development
antivirulants.
Microbial
pathogens
rely
on
their
virulence
factors
initiate
and
sustain
infections.
Antivirulants
are
small
molecules
designed
target
factors,
thereby
attenuating
microbes.
bacterial
type
IV
pilus
(T4P),
an
extracellular
protein
filament
that
depends
T4P
machinery
(T4PM)
its
biogenesis,
dynamics
function,
is
a
key
factor
in
many
significant
pathogens.
While
T4PM
presents
promising
antivirulence
target,
systematic
identification
inhibitors
multiple
constituents
remains
considerable
challenge.
Here
we
report
novel
high-throughput
screening
(HTS)
approach
discovering
inhibitors.
It
uses
Pseudomonas
aeruginosa,
high-priority
pathogen,
combination
with
T4P-targeting
phage,
φKMV.
Screening
library
2168
compounds
using
optimised
protocol
led
tuspetinib,
based
deterrence
lysis
P.
aeruginosa
by
Our
findings
show
tuspetinib
also
inhibits
two
additional
phages,
while
having
no
effect
phage
recognises
lipopolysaccharides
as
receptor.
Additionally,
impedes
T4P-mediated
motility
Acinetobacter
species
without
impacting
growth
or
flagellar
motility.
This
bacterium-phage
pairing
applicable
broad
range
required
infection,
paving
ways
advanced
chemotherapeutics
against
antibiotic-resistant
Microbiology Spectrum,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 6, 2025
ABSTRACT
N
-acetylcysteine
(NAC)
and
ambroxol
hydrochloride
(AMB)
are
commonly
prescribed
alongside
antibiotics
to
alleviate
sputum
retention
in
lower
respiratory
tract
infections,
which
often
caused
by
bacterial
pathogens.
With
the
rising
threat
of
antibiotic
resistance,
phage
therapy
has
emerged
as
a
promising
alternative
alongside.
However,
no
studies
have
explored
potential
interactions
between
phages
these
mucoactive
agents
despite
their
frequent
concurrent
use
during
therapy.
Therefore,
investigating
synergy
its
subsequent
impact
on
infection
dynamics
could
enhance
clinical
strategies
for
treating
infections
with
phages.
Our
study
utilized
Pseudomonas
aeruginosa
strain
ZS-PA-35
Klebsiella
pneumoniae
Kp36,
respective
phages,
investigate
presence
NAC
or
AMB.
findings
indicate
that,
under
specific
conditions,
can
function
adjuvants
lytic
enhancing
susceptibility
facilitating
proliferation.
revealed
that
synergistic
strongly
influenced
physiological
characteristics
surrounding
microenvironments,
physiology
host
tissues,
varying
outcomes
phage-host
were
observed
among
different
across
distinct
media.
Taken
together,
our
results
emphasize
complexity
AMB,
underscoring
need
caution
when
using
combination
treatments.
IMPORTANCE
used
medical
treatment
patients
acute
chronic
bronchitis.
Often,
choice
AMB
is
empirically
determined
physicians.
combining
remains
unclear.
To
address
this
gap,
comprehensive
understanding
interplay
crucial
determine
any
effects.
This
aims
elucidate
how
influence
targeting
receptors,
thereby
affecting
antibacterial
activity
against
.
suggest
certain
provides
an
adjuvant
effect
rendering
cells
more
susceptible
infection.
These
contribute
advancing
therapy,
offering
insights
optimizing
efficacy.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 12, 2025
Abstract
Bacteria
colonize
surfaces
through
complex
mechanisms
of
surface
sensing.
Pili
are
dynamic
bacterial
appendages
that
play
an
important
role
in
this
process.
In
Caulobacter
crescentus
,
tension
on
retracting,
surface-bound
pili
triggers
the
rapid
synthesis
adhesive
holdfast,
which
permanently
attaches
cells
to
surfaces.
However,
detailed
pilus-mediated
sensing
unclear.
study,
we
used
a
genetic
screen
isolate
mutants
with
altered
pilus
activity
identify
genes
may
be
involved
surface-sensing.
This
identified
cpaL
whose
deletion
led
reduced
piliation
levels,
and
surprisingly,
threefold
increase
adhesion
due
increased
holdfast
production.
To
understand
finding,
compared
wild-type
mutant
under
conditions
block
retraction.
While
treatment
production
by
triggering
surface-sensing
pathway,
no
was
observed
mutant,
suggesting
mutation
maximally
stimulates
Furthermore,
when
grown
medium
blocks
exhibited
decreased
attachment
production,
consistent
for
CpaL
pilus-dependent
C.
.
better
function
CpaL,
analyzed
its
predicted
structure,
suggested
is
minor
pilin
fused
mechanosensitive
von
Willebrand
factor
type
A
(vWA)
domain
could
accommodated
at
tip.
These
results
collectively
position
as
strong
candidate
mechanosensory
element
Importance
Surface
crucial
mechanism
allows
bacteria
change
their
behaviors
adapt
life
surface.
recognition
initial
step
toward
colonization
biofilm
formation.
tight
adherence
(Tad)
key
adaptation.
proteins
influence
process
remain
unknown.
Here,
demonstrate
potential
tip
protein,
major
Tad
plays
regulation
upon
contact.
By
identifying
player
recognition,
our
work
offers
valuable
insights
into
adhesion.
mLife,
Journal Year:
2025,
Volume and Issue:
4(1), P. 83 - 95
Published: Feb. 1, 2025
Abstract
In
Pseudomonas
aeruginosa
,
the
dynamic
activity
of
type
IV
pilus
(TFP)
is
essential
for
various
bacterial
behaviors.
While
PilU
considered
a
homolog
TFP
disassembling
motor
PilT,
its
specific
roles
remain
unclear.
Using
visualization
and
single‐cell
tracking
techniques,
we
characterized
dynamics
surface
behaviors
in
wild‐type
Δ
pilU
mutants.
We
found
that
cells
displayed
increased
numbers
but
reduced
cell
movement
delayed
microcolony
formation.
Interestingly,
beyond
affecting
twitching
motility,
formed
thick
multilayered
colony
edge
on
semi‐solid
surfaces,
slowing
expansion.
Cell–cell
collision
responses
changed
from
touch‐turn
dominance
wild
to
touch‐upright
morphology
These
findings
expand
our
understanding
PilU's
physiological
provide
potential
targets
developing
strategies
control
P.
biofilm
formation
virulence.
Applied and Environmental Microbiology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 4, 2025
ABSTRACT
Quorum
sensing
(QS)
plays
a
crucial
role
in
regulating
key
traits,
including
the
upregulation
of
phage
receptors,
which
leads
to
heightened
susceptibility
Pseudomonas
aeruginosa
.
As
result,
higher
cell
densities
typically
increase
risk
invasions.
This
has
led
speculation
that
bacteria
may
have
evolved
strategies
counterbalance
this
increased
susceptibility.
Additionally,
non-synonymous
mutations
LasR,
master
regulator
QS,
are
common
among
cystic
fibrosis
patients,
but
impact
these
on
interactions
remains
poorly
understood.
Here,
we
systematically
investigated
QS
shaping
using
bacterial
strains
with
functional
or
altered
systems.
In
QS-functional
strain
ZS-PA-35,
disruption
Las
system
reduces
type
IV
pili-dependent
phipa2,
delaying
lysis
during
early
logarithmic
growth
phase.
At
high
densities,
Las-induced
dormancy
further
inhibits
proliferation
despite
enhanced
adsorption.
Notably,
nutrient
supplementation
fully
restores
system.
contrast,
QS-deficient
ZS-PA-05,
carrying
LasR
mutation,
fails
regulate
phage-host
via
QS.
Moreover,
our
findings
reveal
within
mixed
microbial
populations,
cells
benefit
from
presence
closely
related
kin,
collectively
reduce
prey
density
and
limit
interaction
frequencies
under
nutrient-rich
conditions.
These
results
underscore
flexibility
QS-regulated
defense
strategies,
highlighting
their
critical
optimizing
resilience
against
predation,
particularly
heterogeneous
communities
most
vulnerable
phages.
IMPORTANCE
Bacteria
developed
various
combat
infection,
posing
challenges
therapy.
study,
demonstrate
quorum
systems
adapt
different
survival
tactics
for
prolonged
coexistence
phages,
contingent
upon
population
dynamics.
The
dynamics
infection
highlight
influence
intrinsic
heterogeneity
mediated
by
emergence
outcomes.
variants
arise
as
result
coevolutionary
processes
mechanisms
mutational
non-mutational
strategies.
insights
enhance
comprehension
how
shield
themselves
attacks
complexity
such
approaches
successful
therapeutic
interventions.
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(4), P. 459 - 459
Published: March 21, 2025
Type
IV
pili
(T4P)
machinery
is
critical
for
bacterial
surface
motility,
protein
secretion,
and
DNA
uptake.
This
review
highlights
the
ecological
significance
of
T4P-dependent
motility
in
Thermus
thermophilus,
a
thermophilic
bacterium
isolated
from
hot
springs.
Unlike
swimming
T4P
enables
bacteria
to
move
over
two-dimensional
surfaces
through
repeated
cycles
extension
retraction
pilus
filaments.
Notably,
T.
thermophilus
exhibits
upstream-directed
migration
under
shear
stress,
known
as
rheotaxis,
which
appears
represent
an
adaptive
strategy
unique
thriving
rapid
water
flows.
Furthermore,
contributes
capture
phages,
indicating
their
multifunctionality
natural
environments.
Understanding
dynamics
provides
insights
into
survival
evolution
extreme
habitats.