bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
ABSTRACT
Antimicrobial
resistance
(AMR)
is
an
important
threat
to
public
health
that
has
led
the
development
of
innovative
alternative
treatments
for
bacterial
infections,
such
as
phage
therapy.
However,
one
greatest
disadvantages
therapy
generation
phage-resistant
mutants
via
defence
mechanisms,
which
are
mainly
contained
in
genomic
islands
(GIs)
and
controlled
by
quorum
sensing
(QS)
network.
In
this
study,
309
pathogenic
(PAIs)
harbouring
a
total
22.1
%
proteins
related
anti-phage
(APD)
were
detected
genome
48
K.
pneumoniae
strains.
Several
type
I
II
CBASS
systems
also
strains,
but
only
2
located
PAIs.
We
constructed
knockout
strain,
not
expressing
cyclase
gene
from
system
present
PAIs,
study
regulatory
role
QS
gene.
As
abortive
infection
(Abi)
system,
regulating
cell
viability
was
assessed.
The
strain
confirmed
targeting
LAMP-CRISPR-Cas13a
technique
specifically
gene,
same
protocol
used
detect
main
these
systems,
i.e.
APECO1.
findings
demonstrate
network
systems.
Finally,
first
work
biotechnological
application
rapid-technique
(<2
hours)
optimizing
detecting
predicting
potential
inefficacy
therapeutic
thus
improving
patient
prognosis.
Nucleic Acids Research,
Год журнала:
2024,
Номер
53(1)
Опубликована: Дек. 9, 2024
Abstract
The
co-evolution
of
prokaryotes,
phages
and
mobile
genetic
elements
(MGEs)
has
driven
the
diversification
defense
anti-defense
systems
alike.
Anti-defense
proteins
have
diverse
functional
domains,
sequences
are
typically
small,
creating
a
challenge
to
detect
homologs
across
prokaryotic
phage
genomes.
To
date,
no
tools
comprehensively
annotate
within
desired
sequence.
Here,
we
developed
‘AntiDefenseFinder’—a
free
open-source
tool
web
service
that
detects
156
one
or
more
in
any
genomic
Using
this
dataset,
identified
47
981
distributed
prokaryotes
their
viruses.
We
found
some
genes
co-localize
‘anti-defense
islands’,
including
Escherichia
coli
T4
Lambda
phages,
although
many
appear
standalone.
Eighty-nine
per
cent
localize
only
preferentially
MGE.
However,
>80%
anti-Pycsar
protein
1
(Apyc1)
resides
nonmobile
regions
bacterial
Evolutionary
analysis
biochemical
experiments
revealed
Apyc1
likely
originated
bacteria
regulate
cyclic
nucleotide
(cNMP)
signaling,
but
co-opted
overcome
cNMP-utilizing
defenses.
With
AntiDefenseFinder
tool,
hope
facilitate
identification
full
repertoire
MGEs,
discovery
new
functions
deeper
understanding
host–pathogen
arms
race.
Virus Research,
Год журнала:
2025,
Номер
352, С. 199524 - 199524
Опубликована: Янв. 8, 2025
The
phyllosphere
microbiome
can
positively
or
negatively
impact
plant
health
and
growth,
but
we
currently
lack
the
tools
to
control
composition.
Contributing
a
growing
collection
of
bacteriophages
(phages)
targeting
bacteria
living
in
wheat
phyllosphere,
here
isolate
sequence
eight
novel
phages
common
Erwinia
Pseudomonas
strains,
including
two
jumbo
phages.
We
characterize
genomic,
phylogenetic,
morphological
traits
from
these
argue
for
establishing
four
viral
genera.
also
search
genomes
anti-defense
systems
investigate
DNA
modifications
using
Nanopore
sequencing.
In
phage
Rembedalsseter
find
evidence
13
motif-associated
single-stranded
breaks.
A
bioinformatics
revealed
that
60
related
are
enriched
same
motif,
suggesting
nicks
may
be
widely
distributed
this
family
Finally,
Sequence
Read
Archive
similar
public
metagenomes.
close
hits
jumbo-phage
Kaldavass
wide
variety
plant,
food,
wastewater
metagenomes
near-perfect
hit
Spanish
spinach
sample,
illustrating
how
interconnected
geographically
distant
be.
Polymers,
Год журнала:
2025,
Номер
17(3), С. 417 - 417
Опубликована: Фев. 5, 2025
Despite
wide
applications
of
CRISPR/Cas9
technology,
effective
approaches
for
CRISPR
delivery
with
functional
control
are
limited.
In
an
attempt
to
develop
a
nanoscale
CRSIPR/Cas9
platform,
we
discovered
that
several
biocompatible
polymers,
including
polymalic
acid
(PMLA),
polyglutamic
(PGA),
and
polyaspartic
(PLD),
when
conjugated
trileucine
(LLL)
moiety,
can
effectively
inhibit
Cas9
nuclease
function.
The
inhibition
by
those
polymers
is
dose-dependent,
varying
efficiency
achieve
100%
inhibition.
Further
biophysical
studies
revealed
PMLA-LLL
directly
binds
the
protein,
resulting
in
substantial
decrease
Cas9/sgRNA
binding
affinity.
Transmission
electron
microscopy
molecular
docking
were
performed
provide
possible
mechanism
interact
Cas9.
This
work
identified
new
class
inhibitor
nano-polymer
form.
These
biodegradable
may
serve
as
novel
vehicles
potential
enhance
precision
Cas9-mediated
gene
editing.
Frontiers in Microbiology,
Год журнала:
2025,
Номер
16
Опубликована: Март 24, 2025
Introduction
Antimicrobial
resistance
(AMR)
is
a
major
public
health
threat,
driving
the
need
for
alternative
treatments
such
as
phage
therapy.
However,
bacterial
defense
mechanisms,
often
regulated
by
quorum
sensing
(QS)
network
and
encoded
in
genomic
islands
(GIs),
can
generate
phage-resistant
mutants.
Understanding
these
mechanisms
essential
optimizing
Methods
This
study
analyzed
48
Klebsiella
pneumoniae
strains
to
identify
pathogenicity
(PAIs)
containing
anti-phage
(APD)
proteins.
We
constructed
knockout
strain
lacking
cyclase
gene
from
type
II
CBASS
systems
present
PAIs
investigate
QS
regulation
its
role
cell
viability.
The
LAMP-CRISPR-Cas13a
technique
was
used
confirm
detect
main
I
systems,
i.e.,
APECO1.
Results
A
total
of
309
(PAIs),
22.1%
proteins,
were
identified.
Type
APD
also
detected
genome
48,
K.
strains,
only
two
located
PAIs.
Alluding
revealed
be
involved
contained
Finally,
technology
successfully
cyclases
habored
respectively.
Discussion
findings
highlight
regulatory
systems.
Notably,
this
first
develop
an
innovative
biotechnological
application
rapid-technique
(<2
h),
thereby
helping
optimize
therapy
detecting
predicting
potential
inefficacy
therapeutic
phages
thus
improving
patient
prognosis.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 21, 2024
The
co-evolution
of
prokaryotes,
phages,
and
mobile
genetic
elements
(MGEs)
over
the
past
billions
years
has
driven
emergence
diversification
defense
anti-defense
systems
alike.
Anti-defense
proteins
have
diverse
functional
domains,
sequences,
are
typically
small,
creating
a
challenge
to
detect
homologs
across
prokaryotic
genomes.
To
date,
no
tools
comprehensively
annotate
within
desired
genome
or
MGE.
Here,
we
developed
"AntiDefenseFinder"
-
free
open-source
tool
web
service
that
detects
156
(of
one
more
proteins)
in
any
genomic
sequence.
Using
this
dataset,
identified
47,981
distributed
phage,
MGEs.
We
found
some
genes
co-localize
"anti-defense
islands",
including
E.
coli
T4
Lambda
although
many
standalone.
Out
112
detected
bacteria,
100
localize
only
preferentially
prophages,
plasmids,
phage
satellites,
integrons,
integrative
conjugative
elements.
However,
80%
anti-Pycsar
protein
1
(Apyc1)
resides
non-mobile
regions
bacteria.
Evolutionary
analyses
revealed
Apyc1
likely
originated
bacteria
regulate
cNMP
signaling,
but
was
co-opted
multiple
times
by
phages
overcome
cNMP-utilizing
defenses.
With
AntiDefenseFinder
tool,
hope
facilitate
identification
full
repertoire
MGEs,
discovery
new
functions,
deeper
understanding
host-pathogen
arms
race.
iScience,
Год журнала:
2024,
Номер
27(9), С. 110791 - 110791
Опубликована: Авг. 23, 2024
Probiotics
typically
refer
to
microorganisms
that
have
been
identified
for
their
health
benefits,
and
they
are
added
foods
or
supplements
promote
the
of
host.
A
growing
number
probiotic
strains
lately
developed
into
valuable
regulatory
pharmaceuticals
nutritional
medical
applications.
Gene
editing
technologies
play
a
crucial
role
in
addressing
need
safe
therapeutic
probiotics
disease
treatment.
These
offer
assistance
comprehending
underlying
mechanisms
bioactivity
development
advanced
probiotics.
This
review
aims
comprehensive
overview
gene
applied
engineering
both
traditional
next-generation
It
further
explores
potential
on-demand
production
customized
products
derived
from
enhanced
probiotics,
with
particular
emphasis
on
future
live
biotherapeutics.
