Nature,
Год журнала:
2023,
Номер
623(7989), С. 1001 - 1008
Опубликована: Ноя. 15, 2023
Cyclic
oligonucleotide-based
antiphage
signalling
systems
(CBASS)
protect
prokaryotes
from
viral
(phage)
attack
through
the
production
of
cyclic
oligonucleotides,
which
activate
effector
proteins
that
trigger
death
infected
host1,2.
How
bacterial
cyclases
recognize
phage
infection
is
not
known.
Here
we
show
staphylococcal
phages
produce
a
structured
RNA
transcribed
terminase
subunit
genes,
termed
CBASS-activating
bacteriophage
(cabRNA),
binds
to
positively
charged
surface
CdnE03
cyclase
and
promotes
synthesis
dinucleotide
cGAMP
CBASS
immune
response.
Phages
escape
defence
harbour
mutations
lead
generation
longer
form
cabRNA
cannot
CdnE03.
As
mammalian
OAS1
also
double-stranded
during
interferon
response,
our
results
reveal
conserved
mechanism
for
activation
innate
antiviral
pathways.
Plants
coordinately
use
cell-surface
and
intracellular
immune
receptors
to
perceive
pathogens
mount
an
response.
Intracellular
events
of
pathogen
recognition
are
largely
mediated
by
the
nucleotide
binding
leucine
rich-repeat
(NLR)
classes.
Upon
perception,
NLRs
trigger
a
potent
broad-spectrum
reaction,
usually
accompanied
form
programmed
cell
death
termed
hypersensitive
Some
plant
act
as
multifunctional
singleton
which
combine
detection
signaling.
However,
can
also
function
in
higher
order
pairs
networks
functionally
specialized
interconnected
receptors.
In
this
article,
we
cover
basic
aspects
NLR
biology
with
emphasis
on
networks.
We
highlight
some
recent
advances
structure,
function,
activation
discuss
emerging
topics
such
modulator
NLRs,
suppression
bioengineering.
Multi-disciplinary
approaches
required
disentangle
how
these
receptor
evolve.
Answering
questions
holds
potential
deepen
our
understanding
system
unlock
new
era
disease
resistance
breeding.
Toll/interleukin-1
receptor
(TIR)
domain
proteins
function
in
cell
death
and
immunity.
In
plants
bacteria,
TIR
domains
are
often
enzymes
that
produce
isomers
of
cyclic
adenosine
5′-diphosphate–ribose
(cADPR)
as
putative
immune
signaling
molecules.
The
identity
functional
conservation
cADPR
isomer
signals
is
unclear.
A
previous
report
found
a
plant
could
cross-activate
the
prokaryotic
Thoeris
TIR–immune
system,
suggesting
TIR-immune
signals.
Here,
we
generate
autoactive
TIRs
test
converse
hypothesis:
Do
also
immunity?
Using
planta
vitro
assays,
find
overlapping
sets
further
clarify
how
activate
system
via
producing
3′cADPR.
This
study
demonstrates
requirements
for
systems
distinct
across
kingdoms
diversity
small-molecule
products.
Annual Review of Virology,
Год журнала:
2023,
Номер
10(1), С. 423 - 453
Опубликована: Июнь 29, 2023
Host
defense
against
viral
pathogens
is
an
essential
function
for
all
living
organisms.
In
cell-intrinsic
innate
immunity,
dedicated
sensor
proteins
recognize
molecular
signatures
of
infection
and
communicate
to
downstream
adaptor
or
effector
activate
immune
defense.
Remarkably,
recent
evidence
demonstrates
that
much
the
core
machinery
immunity
shared
across
eukaryotic
prokaryotic
domains
life.
Here,
we
review
a
pioneering
example
evolutionary
conservation
in
immunity:
animal
cGAS-STING
(cyclic
GMP-AMP
synthase-stimulator
interferon
genes)
signaling
pathway
its
ancestor
bacteria,
CBASS
nucleotide-based
antiphage
system)
We
discuss
unique
mechanism
by
which
cGLRs
(cGAS-like
receptors)
bacterial
CD-NTases
(cGAS/dinucleotide-cyclase
Vibrio
(DncV)-like
nucleotidyltransferases)
these
pathways
link
pathogen
detection
with
activation
using
nucleotide
second
messenger
signals.
Comparing
biochemical,
structural,
mechanistic
details
cGAS-STING,
cGLR
signaling,
CBASS,
highlight
emerging
questions
field
examine
pressures
may
have
shaped
origins
antiviral
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 1, 2024
Abstract
Cell-surface
receptors
play
pivotal
roles
in
many
biological
processes,
including
immunity,
development,
and
reproduction,
across
diverse
organisms.
How
cell-surface
evolve
to
become
specialised
different
processes
remains
elusive.
To
shed
light
on
the
immune-specificity
of
receptors,
we
analyzed
more
than
200,000
genes
encoding
from
350
genomes
traced
evolutionary
origin
immune-specific
leucine-rich
repeat
receptor-like
proteins
(LRR-RLPs)
plants.
Surprisingly,
discovered
that
motifs
crucial
for
co-receptor
interaction
LRR-RLPs
are
closely
related
those
LRR-receptor-like
kinase
(RLK)
subgroup
Xb,
which
perceives
phytohormones
primarily
governs
growth
development.
Functional
characterisation
further
reveals
initiate
immune
responses
through
their
juxtamembrane
transmembrane
regions,
while
LRR-RLK-Xb
members
regulate
development
cytosolic
domains.
Our
data
suggest
involved
immunity
share
a
common
origin.
After
diversification,
ectodomains,
juxtamembrane,
transmembrane,
regions
have
either
diversified
or
stabilised
recognise
ligands
activate
differential
downstream
responses.
work
mechanism
by
plants
perceive
signals
appropriate
rapidly
changing
environment.
Prokaryotes
encode
multiple
distinct
anti-phage
defense
systems
in
their
genomes.
However,
the
impact
of
carrying
a
multitude
on
phage
resistance
remains
unclear,
especially
clinical
context.
Using
collection
antibiotic-resistant
strains
Pseudomonas
aeruginosa
and
broad
panel
phages,
we
demonstrate
that
contribute
substantially
to
defining
host
range
overall
scales
with
number
bacterial
genome.
We
show
many
individual
target
specific
genera
complementary
specificities
co-occur
P.
genomes
likely
provide
benefits
phage-diverse
environments.
Overall,
phage-resistant
phenotypes
at
least
19
exist
populations
clinical,
strains.
Trends in Microbiology,
Год журнала:
2024,
Номер
32(12), С. 1212 - 1228
Опубликована: Июнь 5, 2024
The
biological
interplay
between
phages
and
bacteria
has
driven
the
evolution
of
phage
anti-defence
systems
(ADSs),
which
evade
bacterial
defence
mechanisms.
These
ADSs
bind
inhibit
host
proteins,
add
covalent
modifications
deactivate
degrade
or
sequester
signalling
molecules
utilised
by
systems,
synthesise
restore
essential
depleted
defences,
to
avoid
recognition.
Overall,
145
have
been
characterised
date.
counteract
27
152
different
families,
we
hypothesise
that
many
more
are
yet
be
discovered.
We
discuss
high-throughput
approaches
(computational
experimental)
indispensable
for
discovering
new
limitations
these
approaches.
A
comprehensive
characterisation
is
critical
understanding
phage–host
developing
clinical
applications,
such
as
treatment
multidrug-resistant
infections.
Science,
Год журнала:
2025,
Номер
387(6733), С. 510 - 516
Опубликована: Янв. 30, 2025
Caspase
family
proteases
and
Toll/interleukin-1
receptor
(TIR)-domain
proteins
have
central
roles
in
innate
immunity
regulated
cell
death
humans.
We
describe
a
bacterial
immune
system
comprising
both
caspase-like
protease
TIR-domain
protein.
found
that
the
TIR
protein,
once
it
recognizes
phage
invasion,
produces
previously
unknown
signaling
molecule
adenosine
5′-diphosphate-cyclo[N7:1′′]-ribose
(N7-cADPR).
This
specifically
activates
protease,
which
then
indiscriminately
degrades
cellular
to
halt
replication.
The
TIR-caspase
defense
system,
we
denote
as
type
IV
Thoeris,
is
abundant
bacteria
efficiently
protects
against
propagation.
Our
study
highlights
diversity
of
TIR-produced
molecules
demonstrates
by
caspase
an
ancient
mechanism
immunity.