bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 11, 2024
Abstract
Understanding
the
human
gut
microbiome
requires
comprehensive
genomic
catalogs,
yet
many
existing
ones
lack
geographic
diversity
and
include
numerous
medium-quality
metagenome-assembled
genomes
(MAGs)
missing
up
to
50%
of
regions,
potentially
leading
inaccurate
functional
insights
into
microbiome.
To
address
these
limitations,
we
developed
an
enhanced
Human
Reference
Gut
Microbiome
(HRGM2),
a
catalog
near-complete
(NC)
MAGs
(completeness
≥90%
contamination
≤5%)
isolate
(collectively
‘NC
genomes’)
with
extensive
sampling.
HRGM2
comprises
155,211
non-redundant
NC
from
4,824
prokaryotic
species
across
41
countries,
representing
66%
increase
in
genome
count
boost
over
genome-based
Unified
Gastrointestinal
Genome
catalog.
Extensive
sampling
Africa
revealed
previously
undetectable
Africa-associated
phyla,
highlighting
microbial
links
between
humans
environment.
Given
high
complexity
microbiota,
DNA-based
profiling
using
outperforms
marker-based
accuracy.
Profiling
protein
annotations
provides
reliable
Notably,
exclusive
use
genomes,
enhances
assessments
microbiota
metabolic
capacities
supports
genome-scale
models
(GEMs)
entire
microbiota.
These
findings
offer
novel
perspectives
on
microbiome,
achievable
only
through
high-quality
cataloging.
Nature Microbiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 10, 2025
Abstract
Gut
bacteria
from
the
Enterobacteriaceae
family
are
a
major
cause
of
opportunistic
infections
worldwide.
Given
their
prevalence
among
healthy
human
gut
microbiomes,
interspecies
interactions
may
play
role
in
modulating
infection
resistance.
Here
we
uncover
global
ecological
patterns
linked
to
colonization
and
abundance
by
leveraging
large-scale
dataset
12,238
public
metagenomes
spanning
45
countries.
Machine
learning
analyses
identified
robust
microbiome
signature
associated
with
status,
consistent
across
health
states
geographic
locations.
We
classified
172
microbial
species
as
co-colonizers
135
co-excluders,
revealing
genus-wide
signal
resistance
within
Faecalibacterium
strain-specific
co-colonization
underexplored
Faecalimonas
phoceensis
.
Co-exclusion
is
functions
involved
short-chain
fatty
acid
production,
iron
metabolism
quorum
sensing,
while
greater
functional
diversity
metabolic
resemblance
Enterobacteriaceae.
Our
work
underscores
critical
intestinal
environment
success
gut-associated
pathogens
implications
for
developing
non-antibiotic
therapeutic
strategies.
The
human
gastrointestinal
tract
is
colonized
by
a
complex
microbial
ecosystem,
the
gut
microbiota,
which
pivotal
in
maintaining
host
health
and
mediating
resistance
to
diseases.
This
review
delineates
colonization
(CR),
critical
defensive
mechanism
employed
microbiota
safeguard
against
pathogenic
bacterial
invasions,
notably
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 9, 2025
Abstract
Competition
among
bacteria
for
carbohydrates
is
pivotal
colonization
resistance
(CR).
However,
the
impact
of
Western-style
diets
on
CR
remains
unclear.
Here
we
show
how
competition
between
Klebsiella
oxytoca
and
pneumoniae
modulated
by
consuming
one
three
characterized
high-starch,
high-sucrose,
or
high-fat/high-sucrose
content.
In
vivo
experiments
in
ampicillin-treated
mice
reveal
that
K.
promotes
decolonization
all
dietary
backgrounds.
diet
reduced
pathogen
clearance.
Microbiome
analysis
reveals
combination
ampicillin
treatment
synergize
microbiome
impairment,
particularly
noticeable
presence
high
fat
The
diet-independent
degradation
gut
lumen
beta-lactamases
facilitates
rapid
commensal
outgrowth,
which
required
subsequent
Our
findings
provide
insights
into
modulates
functional
recovery
-mediated
elimination
from
gut.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 5, 2025
Antimicrobial
peptides
SAAP-148
exhibited
excellent
antimicrobial
activities
but
suffered
from
inherent
disadvantages,
including
cytotoxicity
and
poor
proteolytic
stability.
Herein,
we
developed
a
novel
strategy
combining
one
unique
silver-catalyzed
solid-phase
glycosylation-enabled
arginine
N-glycosylation
all-hydrocarbon
peptide
double-stapling,
five-round
libraries
were
rationally
constructed
containing
over
50
stapled
and/or
N-glycosylated
peptides.
SLP-51
consisting
of
two
introduced
staples
the
C-terminal
glycosylation
superior
in
vitro
against
drug-resistant
Gram-positive
or
-negative
clinical
isolates.
also
improved
stability
than
parent
SLP-0,
importantly,
significantly
weakened
hemolysis.
Experimental
modeling
mechanism
research
indicated
that
exerted
similar
stronger
killing
abilities
by
destroying
integrality
bacterial
membranes.
In
both
skin
wound
pneumonia
models,
showcased
potent
therapeutic
effect
treating
MRSA
Klebsiella
pneumoniae
infection
vivo
dramatical
improvement
inflammatory
injury.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 6, 2025
Abstract
Quorum
sensing
(QS)
is
the
communication
system
of
bacteria
that
depends
on
QS
signals.
quenching
(QQ)
enzymes
degrade
signals
and
are
promising
alternatives
antibiotics
to
treat
bacterial
infections.
Here,
we
found
dietary
QQ
N
-acyl
homoserine
(AHL)
lactonase
led
microbiota
dysbiosis
in
zebrafish,
with
reduction
Aeromonas
enrichment
Plesiomonas
.
Through
gnotobiotic
zebrafish
colonized
a
minimal
microbiota,
QQ-mediated
microbial
alteration
relies
host
Myd88
signaling
neutrophil
elastase.
Mechanistically,
quorum
increased
susceptibility
commensal
elastase
by
impairing
lateral
flagellar
system,
leading
reduced
colonization
subsequent
due
ecological
competition
two
species.
Together,
adaptation
innate
immunity,
which
provided
novel
insight
role
host-microbiota
interaction.