RNA interactome of hypervirulent Klebsiella pneumoniae reveals a small RNA inhibitor of capsular mucoviscosity and virulence
Kejing Wu,
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Xingyu Lin,
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Yujie Lu
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et al.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 13, 2024
Hypervirulent
Klebsiella
pneumoniae
(HvKP)
is
an
emerging
bacterial
pathogen
causing
invasive
infection
in
immune-competent
humans.
The
hypervirulence
strongly
linked
to
the
overproduction
of
hypermucoviscous
capsule,
but
underlying
regulatory
mechanisms
hypermucoviscosity
(HMV)
have
been
elusive,
especially
at
post-transcriptional
level
mediated
by
small
noncoding
RNAs
(sRNAs).
Using
a
recently
developed
RNA
interactome
profiling
approach
iRIL-seq,
we
interrogate
Hfq-associated
sRNA
network
and
establish
intracellular
RNA-RNA
HvKP.
Our
data
reveal
numerous
interactions
between
sRNAs
HMV-related
mRNAs,
identify
plethora
that
repress
or
promote
HMV.
One
strongest
HMV
repressors
ArcZ,
which
activated
catabolite
regulator
CRP
targets
many
genes
including
mlaA
fbp.
We
discover
MlaA
its
function
phospholipid
transport
crucial
for
capsule
retention
HMV,
inactivation
abolishes
virulence
mice.
ArcZ
overexpression
drastically
reduces
burden
mice
multiple
hypervirulent
carbapenem-resistant
clinical
isolates,
indicating
potent
inhibitor
pneumonia
with
therapeutic
potential.
work
unravels
novel
CRP-ArcZ-MlaA
circuit
provides
mechanistic
insights
into
posttranscriptional
control
superbug
global
concern.
By
performing
analysis
pneumoniae,
authors
key
factor
MlaA,
inhibiting
pathogenesis
Language: Английский
Invasive bacteriophages between a bell and a hammer: a comprehensive review of pharmacokinetics and bacterial defense systems
Mohammed F Hamdi,
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Alyaa Abdulhussein Alsaedi,
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Alaa Qasim Hayder
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et al.
Discover Life,
Journal Year:
2025,
Volume and Issue:
55(1)
Published: April 3, 2025
Language: Английский
Non-genetic messenger RNA silencing reveals essential genes in phage-host interplay
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 31, 2024
Bacteriophages
are
the
most
abundant
entities
on
earth
and
exhibit
vast
genetic
phenotypic
diversity.
Exploitation
of
this
largely
unexplored
molecular
space
requires
identification
functional
characterisation
genes
that
act
at
phage-host
interface.
To
date,
is
restricted
to
few
model
systems
amenable
manipulation.
overcome
limitation,
we
introduce
a
non-genetic
mRNA
targeting
approach
using
exogenous
delivery
programmable
antisense
oligomers
(ASOs)
silence
both
DNA
RNA
phages.
A
systematic
knockdown
screen
core
accessory
nucleus-forming
jumbo
phage
ΦKZ,
coupled
RNA-sequencing
microscopy
analyses,
reveals
previously
unrecognised
proteins
essential
for
replication
that,
upon
silencing,
elicit
distinct
phenotypes
level
host
response.
One
these
factors
ΦKZ-encoded
nuclease
acts
major
decision
point
during
infection,
linking
formation
protective
nucleus
genome
amplification.
The
ASO-based
gene
silencing
used
here
promises
be
versatile
tool
discovery
in
biology,
will
help
elucidate
defence
anti-defence
mechanisms
non-model
pairs,
offers
potential
optimising
therapy
biotechnological
procedures.
Language: Английский
A review on the crosstalk between non-coding RNAs and the cGAS-STING signaling pathway
International Journal of Biological Macromolecules,
Journal Year:
2024,
Volume and Issue:
283, P. 137748 - 137748
Published: Nov. 19, 2024
Language: Английский
Slings and arrows: sRNAs mediate intragenomic competition
Cell Host & Microbe,
Journal Year:
2024,
Volume and Issue:
32(5), P. 634 - 636
Published: May 1, 2024
Language: Английский
Phage-encoded small RNA hijacks host replication machinery to support the phage lytic cycle
Aviezer Silverman,
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Raneem Nashef,
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Robert Bruner
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et al.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 31, 2024
ABSTRACT
Bacteriophages
(phages)
significantly
influence
bacterial
populations
in
their
natural
environment.
However,
one
aspect
that
has
not
been
thoroughly
explored
the
context
of
phage-bacteria
interactions
is
post-transcriptional
regulation
gene
expression,
despite
growing
recognition
its
importance
physiology
over
past
two
decades.
Important
players
this
process
are
small
RNAs
(sRNAs)
regulate
target
mRNAs
via
base-pairing,
typically
using
RNA
chaperones
like
Hfq
to
facilitate
regulation.
Here,
we
apply
RIL-seq
map
in-vivo
sRNA-RNA
network
Escherichia
coli
upon
lambda
phage
infection.
We
highlight
changes
transcriptome
and
sRNA
interactome
while
uncovering
a
novel
phage-encoded
regulates
key
genes
E.
.
decipher
molecular
mechanism
sRNA-mediated
illustrate
how
hijacks
host
replication
machinery
helps
infection
cycle.
Overall,
uncover
an
RNA-level
regulatory
layer
shapes
-
interactions.
Language: Английский
Biological Insights from RNA–RNA Interactomes in Bacteria, as Revealed by RIL-seq
Aviezer Silverman,
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Sahar Melamed
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Methods in molecular biology,
Journal Year:
2024,
Volume and Issue:
unknown, P. 189 - 206
Published: Nov. 15, 2024
Language: Английский
ProQ-associated small RNAs control motility in Vibrio cholerae
Rabea Ghandour,
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Daniel Devlitsarov,
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Phillip Popp
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et al.
Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 27, 2024
Abstract
Gene
regulation
at
the
post-transcriptional
level
is
prevalent
in
all
domains
of
life.
In
bacteria,
ProQ-like
proteins
have
emerged
as
important
RNA
chaperones
facilitating
stability
and
duplex
formation.
major
human
pathogen
Vibrio
cholerae,
gene
key
for
virulence,
biofilm
formation,
antibiotic
resistance,
yet
role
ProQ
has
not
been
studied.
Here,
we
show
that
interacts
with
hundreds
transcripts
V.
including
highly
abundant
FlaX
small
(sRNA).
Global
analyses
formation
using
RIL-Seq
(RNA
interaction
by
ligation
sequencing)
revealed
a
vast
network
ProQ-assisted
interactions
identified
motility
regulation.
Specifically,
base-pairs
multiple
sites
on
flaB
flagellin
mRNA,
preventing
30S
ribosome
binding
translation
initiation.
cholerae
cells
lacking
flaX
display
impaired
expression,
altered
flagella
composition
reduced
swimming
liquid
environments.
Our
results
provide
global
view
ProQ-associated
pinpoint
mechanistic
phenotypic
consequences
associated
sRNAs
cholerae.
Language: Английский