bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 10, 2024
ABSTRACT
Cyclic
dimeric
GMP
(c-di-GMP)
is
a
widespread
bacterial
second
messenger
that
controls
variety
of
cellular
functions,
including
protein
and
polysaccharide
secretion,
motility,
cell
division,
development,
biofilm
formation,
contributes
to
the
virulence
some
important
pathogens.
While
genes
for
diguanylate
cyclases
c-di-GMP
hydrolases
(active
or
mutated)
can
be
easily
identified
in
microbial
genomes,
list
receptor
domains
quite
limited,
only
two
them,
PliZ
MshEN,
are
found
across
multiple
phyla.
Recently,
new
protein,
named
CdgR
ComFB,
has
been
cyanobacteria
shown
regulate
their
size
and,
more
recently,
natural
competence.
Sequence
structural
analysis
indicated
part
ComFB
family,
after
“late
competence
development
ComFB”
from
Bacillus
subtilis
.
This
prompted
suggestion
ComFB-like
proteins
could
also
receptors.
Indeed,
we
revealed
Gram-positive
B.
Thermoanaerobacter
brockii
were
able
bind
with
high-affinity.
The
ability
was
demonstrated
clinically
relevant
Gram-negative
bacteria
Vibrio
cholerae
Treponema
denticola
These
observations
indicate
family
serves
as
yet
another
Incidentally,
capable
c-di-AMP
binding,
identifying
them
unique
c-di-NMP
proteins.
overexpression
comFB
subtilis,
combined
an
elevated
concentration
c-di-GMP,
suppressed
attesting
biological
relevance
binding
protein.
IMPORTANCE
content
controlled
by
synthases
(GGDEF
domains)
(EAL
HD-GYP
domains),
whose
activities,
turn,
respond
signals
perceived
upstream
sensory
domains.
Cyclic-di-GMP
transmits
its
targets,
which
may
contain
inactivated
GGDEF,
EAL,
domains,
PilZ
MshEN
various
lineage-specific
Many
organisms
encode
GGDEF
but
few
c-di-GMP-binding
proteins,
suggesting
existence
still
unidentified
Here,
demonstrate
include
recently
characterized
cyanobacterial
CdgR/ComFB,
constitute
We
additionally
show
bacillar
motility
c-di-GMP-dependent
manner.
Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
53(D1), P. D356 - D363
Published: Nov. 4, 2024
The
Clusters
of
Orthologous
Genes
(COG)
database,
originally
created
in
1997,
has
been
updated
to
reflect
the
constantly
growing
collection
completely
sequenced
prokaryotic
genomes.
This
update
increased
genome
coverage
from
1309
2296
species,
including
2103
bacteria
and
193
archaea,
most
cases,
with
a
single
representative
per
genus.
set
covers
all
genera
archaea
that
included
organisms
'complete
genomes'
as
NCBI
databases
November
2023.
number
COGs
expanded
4877
4981,
primarily
by
protein
families
involved
bacterial
secretion.
Accordingly,
COG
pathways
functional
groups
now
include
secretion
systems
types
II
through
X,
well
Flp/Tad
type
IV
pili.
These
groupings
allow
straightforward
identification
examination
lineages
encompass-or
lack-a
particular
system.
Other
developments
improved
annotations
for
rRNA
tRNA
modification
proteins,
multi-domain
signal
transduction
some
previously
uncharacterized
families.
new
version
is
available
at
https://www.ncbi.nlm.nih.gov/research/COG,
on
FTP
site
https://ftp.ncbi.nlm.nih.gov/pub/COG/,
which
also
provides
archived
data
previous
releases.
Microbiology and Molecular Biology Reviews,
Journal Year:
2024,
Volume and Issue:
88(2)
Published: June 10, 2024
SUMMARYNucleotide-derived
second
messengers
are
present
in
all
domains
of
life.
In
prokaryotes,
most
their
functionality
is
associated
with
general
lifestyle
and
metabolic
adaptations,
often
response
to
environmental
fluctuations
physical
parameters.
the
last
two
decades,
cyclic
di-AMP
has
emerged
as
an
important
signaling
nucleotide
many
prokaryotic
lineages,
including
Firmicutes,
Actinobacteria,
Cyanobacteria.
Its
importance
highlighted
by
fact
that
both
lack
overproduction
affect
viability
prokaryotes
utilize
di-AMP,
it
generates
a
strong
innate
immune
eukaryotes.
bacteria
produce
messenger,
molecular
targets
cell
volume
control.
Besides,
other
evidence
links
messenger
wall
remodeling,
DNA
damage
repair,
sporulation,
central
metabolism,
regulation
glycogen
turnover.
this
review,
we
take
biochemical,
quantitative
approach
address
main
cellular
processes
directly
regulated
show
these
very
connected
require
similar
set
proteins
which
binds.
Altogether,
argue
master
regulator
can
be
through
core
function.
We
further
highlight
directions
field
develop
gain
full
understanding
network
why
some
regulated,
while
others
not.
Fermentation,
Journal Year:
2025,
Volume and Issue:
11(4), P. 196 - 196
Published: April 7, 2025
Lactic
acid
bacteria
exopolysaccharides
(EPS)
have
a
variety
of
excellent
biological
functions
and
are
widely
used
in
the
food
pharmaceutical
industries.
The
complex
metabolic
system
lactic
mechanism
EPS
biosynthesis
not
been
fully
analyzed,
which
limits
wider
application
EPS.
synthesis
is
regulated
by
cyclic
diadenosine
monophosphate
(c-di-AMP),
but
exact
remains
unclear.
Dac
pde
c-di-AMP
anabolic
genes,
gtfA,
gtfB
gtfC
gene
clusters,
among
was
key
for
Leuconostoc
mesenteroides
DRP105.
In
order
to
explore
whether
diadenylate
cyclase
(DAC)
can
catalyze
from
ATP,
sequence
DAC
analyzed
bioinformatics
based
on
whole
genome
sequence.
CdaA
type
containing
classical
domain
DisA_N
DGA
RHR
motifs.
secondary
structure
mainly
composed
α-helices,
AlphaFold2
model
3D
protein
evaluate
rationality
model.
A
total
8
salt
bridges,
21
hydrogen
bonds
221
non-bonded
interactions
were
found
between
GtfC.
Molecular
docking
simulations
revealed
ATP1
ATP2
occupied
binding
pocket
interacted
directly
with
site
residues
DAC.
molecular
dynamics
showed
that
ATP
molecules
relatively
stable.
Gene
enzyme
correlation
analysis
dac
expression
significantly
positively
correlated
activity,
content
production,
had
no
significant
PDE
activity
responsible
degradation.
Bioinformatics
regulatory
role
helpful
reveal
biosynthetic
provide
theoretical
basis
large-scale
industrial
production
microLife,
Journal Year:
2023,
Volume and Issue:
4
Published: Jan. 1, 2023
Abstract
The
dinucleotide
cyclic
di-AMP
(c-di-AMP)
is
synthesized
as
a
second
messenger
in
the
Gram-positive
model
bacterium
Bacillus
subtilis
well
many
bacteria
and
archaea.
possesses
three
diadenylate
cyclases
two
phosphodiesterases
that
synthesize
degrade
molecule,
respectively.
Among
messengers,
c-di-AMP
unique
since
it
essential
for
B.
on
one
hand
but
toxic
upon
accumulation
other.
This
role
an
“essential
poison”
related
to
function
of
control
potassium
homeostasis.
C-di-AMP
inhibits
expression
activity
uptake
systems
by
binding
riboswitches
transporters
activates
exporters.
In
this
way,
allows
adjustment
export
achieve
balanced
intracellular
concentration.
also
binds
dedicated
signal
transduction
proteins,
DarA
DarB.
Both
proteins
seem
interact
with
other
their
apo
state,
i.e.
absence
c-di-AMP.
For
DarB,
(p)ppGpp
synthetase/hydrolase
Rel
pyruvate
carboxylase
PycA
have
been
identified
targets.
interactions
trigger
synthesis
alarmone
acceptor
molecule
citric
acid
cycle,
oxaloacetate,
c-di-AMP,
amino
acids
inhibit
growth
subtilis.
feature
can
be
used
identify
novel
players
review,
we
discuss
different
functions
physiological
relevance.
Molecular Microbiology,
Journal Year:
2023,
Volume and Issue:
120(6), P. 791 - 804
Published: Oct. 28, 2023
Abstract
Cyclic
dimeric
adenosine
monophosphate
(c‐di‐AMP)
has
been
well
studied
in
bacteria,
including
those
of
the
genus
Streptococcus
,
since
first
recognition
this
dinucleotide
2008.
Streptococci
possess
a
sole
diadenylate
cyclase,
CdaA,
and
distinct
c‐di‐AMP
phosphodiesterases.
Interestingly,
cdaA
is
required
for
viability
some
streptococcal
species
but
not
all
when
streptococci
are
grown
standard
laboratory
media.
Bacteria
also
have
effector
proteins,
diverse
c‐di‐AMP‐signaling
pathways,
subsequent
biological
outcomes.
In
streptococci,
may
influence
bacterial
growth,
morphology,
biofilm
formation,
competence
program,
drug
resistance,
pathogenesis.
secreted
by
shown
to
interact
with
mammalian
host
induces
immune
responses
type
I
interferon
production.
review,
we
summarize
reported
networks
seven
which
cause
clinical
manifestations,
propose
future
perspectives
investigate
signaling
molecule
these
pathogens.
Molecular Oral Microbiology,
Journal Year:
2024,
Volume and Issue:
39(5), P. 354 - 367
Published: March 4, 2024
Pathobionts
associated
with
periodontitis,
such
as
Treponema
denticola,
must
possess
numerous
sensory
transduction
systems
to
adapt
the
highly
dynamic
subgingival
environment.
To
date,
signaling
pathways
utilized
by
T.
denticola
rapidly
sense
and
respond
environmental
stimuli
are
mainly
unknown.
Bis-(3'-5')
cyclic
diadenosine
monophosphate
(c-di-AMP)
is
a
nucleotide
secondary
messenger
that
regulates
osmolyte
transport,
central
metabolism,
biofilm
development,
pathogenicity
in
many
bacteria
but
uncharacterized
denticola.
Here,
we
studied
c-di-AMP
understand
how
it
contributes
physiology.
We
demonstrated
produces
identified
enzymes
function
synthesis
(TDE1909)
hydrolysis
(TDE0027)
of
c-di-AMP.
investigate
may
impact
cellular
processes,
screening
assay
was
performed
identify
putative
receptor
proteins.
This
approach
TDE0087,
annotated
potassium
uptake
protein,
first
binding
protein.
As
homeostasis
critical
for
maintaining
turgor
pressure,
concentrations
impacted
osmolarity,
suggesting
negatively
hypoosmotic
solutions.
Collectively,
this
study
demonstrates
utilizes
signaling,
identifies
metabolism
proteins,
correlates
osmoregulation.
Microbiology Spectrum,
Journal Year:
2024,
Volume and Issue:
12(8)
Published: June 20, 2024
ABSTRACT
The
Gram-positive
bacterium
Bacillus
anthracis
is
the
causative
agent
of
anthrax
and
a
bioterrorism
threat
worldwide.
As
crucial
second
messenger
in
many
bacterial
species,
cyclic
di-AMP
(c-di-AMP)
modulates
various
key
processes
for
homeostasis
pathogenesis.
Overaccumulation
c-di-AMP
alters
cellular
growth
reduces
toxin
expression
as
well
virulence
by
unresolved
underlying
mechanisms.
In
this
report,
we
discovered
that
binds
to
series
receptors
involved
potassium
uptake
B.
.
By
analyzing
Kdp
Ktr
mutants
osmotic
stress,
gene
expression,
also
showed
inhibits
operon
through
binding
KdpD
ydaO
riboswitch;
up-regulating
intracellular
promotes
accumulated
Decreased
at
high
occurs
inhibition
uptake.
Understanding
molecular
basis
how
affects
has
potential
provide
new
insight
into
control
anthracis.
IMPORTANCE
conserved
global
regulator
homeostasis.
How
regulates
unknown.
With
study,
link
between
accumulation
might
inhibit
suppressing