Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 30, 2024
Development
of
potent
and
broad-spectrum
antimicrobial
peptides
(AMPs)
could
help
overcome
the
resistance
crisis.
We
develop
a
peptide
language-based
deep
generative
framework
(deepAMP)
for
identifying
potent,
AMPs.
Using
deepAMP
to
reduce
enhance
membrane-disrupting
abilities
AMPs,
we
identify,
synthesize,
experimentally
test
18
T1-AMP
(Tier
1)
11
T2-AMP
2)
candidates
in
two-round
design
by
employing
cross-optimization-validation.
More
than
90%
designed
AMPs
show
better
inhibition
penetratin
both
Gram-positive
(i.e.,
S.
aureus)
Gram-negative
bacteria
K.
pneumoniae
P.
aeruginosa).
T2-9
shows
strongest
antibacterial
activity,
comparable
FDA-approved
antibiotics.
that
three
(T1-2,
T1-5
T2-10)
significantly
aureus
compared
ciprofloxacin
are
effective
against
skin
wound
infection
female
mouse
model
infected
with
aeruginosa.
In
summary,
expedites
discovery
effective,
drug-resistant
bacteria.
Clinical Microbiology Reviews,
Journal Year:
2021,
Volume and Issue:
35(1)
Published: Dec. 1, 2021
Klebsiella
oxytoca
is
actually
a
complex
of
nine
species-Klebsiella
grimontii,
huaxiensis,
michiganensis,
K.
oxytoca,
pasteurii,
spallanzanii,
and
three
unnamed
novel
species.
Phenotypic
tests
can
assign
isolates
to
the
complex,
but
precise
species
identification
requires
genome-based
analysis.
The
human
commensal
also
an
opportunistic
pathogen
causing
various
infections,
such
as
antibiotic-associated
hemorrhagic
colitis
(AAHC),
urinary
tract
infection,
bacteremia,
has
caused
outbreaks.
Production
cytotoxins
tilivalline
tilimycin
lead
AAHC,
while
many
virulence
factors
seen
in
pneumoniae,
capsular
polysaccharides
fimbriae,
have
been
found
complex;
however,
their
association
with
pathogenicity
remains
unclear.
Among
5,724
clinical
SENTRY
surveillance
system,
rates
nonsusceptibility
carbapenems,
ceftriaxone,
ciprofloxacin,
colistin,
tigecycline
were
1.8%,
12.5%,
7.1%,
0.8%,
0.1%,
respectively.
Resistance
carbapenems
increasing
alarmingly.
In
addition
intrinsic
blaOXY,
genes
encoding
β-lactamases
varying
spectra
hydrolysis,
including
extended-spectrum
β-lactamases,
few
CTX-M
variants
several
TEM
SHV
variants,
found.
blaKPC-2
most
common
carbapenemase
gene
mainly
on
IncN
or
IncF
plasmids.
Due
ability
acquire
antimicrobial
resistance
carriage
multiple
genes,
potential
become
major
threat
health.
Infection and Immunity,
Journal Year:
2021,
Volume and Issue:
89(4)
Published: Feb. 4, 2021
Klebsiella
pneumoniae
are
Gram-negative
facultative
anaerobes
that
found
within
host-associated
commensal
microbiomes,
but
they
can
also
cause
a
wide
range
of
infections
often
difficult
to
treat.
These
caused
by
different
pathotypes
K.
pneumoniae,
called
either
classical
or
hypervirulent
strains.
two
groups
genetically
distinct,
inhabit
nonoverlapping
geographies,
and
types
harmful
in
humans.
distinct
bacterial
have
been
interact
differently
with
the
host
immune
system.
Initial
innate
defenses
against
infection
include
complement,
macrophages,
neutrophils,
monocytes;
these
primary
strategies
employed
clear
infections.
pathogenesis
depends
upon
interactions
between
microbe
each
defenses,
it
is
becoming
increasingly
apparent
genetic
diversity
impacts
outcomes
interactions.
Here,
we
highlight
recent
advances
our
understanding
pathogenesis,
focus
on
how
evolution
impact
mammalian
defenses.
We
discuss
outstanding
questions
regarding
frustrate
normal
responses,
capitalize
states
immunocompromise,
high
mortality.
International Journal of Environmental Research and Public Health,
Journal Year:
2022,
Volume and Issue:
19(22), P. 15345 - 15345
Published: Nov. 20, 2022
Bacteria
are
readily
nourished
in
airtight
environments
with
high
humidity,
such
as
storage
cabinets,
clothing
closets,
and
corners,
where
ventilation
is
normally
low
humidity
high.We
characterized
the
role
of
bacterial
growth
genus
distribution
at
different
temperatures
(26
°C
34
°C).Fresh
pork,
which
was
used
substrate
for
culture,
placed
cabinets.
Bacterial
genera
on
surface
pork
a
cabinet
under
°C);
relative
levels
(RH:
50%,
70%,
90%);
conditions
(no
low,
medium,
ventilation)
were
assessed
by
rDNA
sequencing.Increased
reduced
significantly
decreased
26
°C.
The
contribution
increased
to
reduction
exceeded
that
humidity.
Ventilation
had
greatest
effect
reducing
compared
unventilated
70%
RH.
At
°C,
medium
required
reduce
growth.
High
greatly
growth,
but
could
degree
this
increase.
Infection and Drug Resistance,
Journal Year:
2022,
Volume and Issue:
Volume 15, P. 3589 - 3609
Published: July 1, 2022
Although
antimicrobials
have
traditionally
been
used
to
treat
infections
and
improve
health
outcomes,
resistance
commonly
has
posed
a
major
challenge.
An
estimated
700,000
deaths
occur
globally
every
year
as
result
of
caused
by
antimicrobial-resistant
pathogens.
Antimicrobial
(AMR)
also
contributes
directly
the
decline
in
global
economy.
In
2019,
sub-Saharan
Africa
(SSA)
had
highest
mortality
rate
(23.5
per
100,000)
attributable
AMR
compared
other
regions.We
searched
PubMed
for
articles
relevant
pathogens
WHO-GLASS
list
local
importance
SSA.
this
review,
we
focused
on
rates
surveillance
these
priority
some
most
encountered
public
significance.
addition,
reviewed
implementation
national
action
plans
mitigate
against
countries
SSA.The
SSA
region
is
disproportionately
affected
AMR,
part
owing
prevailing
high
levels
poverty,
which
burden
infectious
diseases,
poor
regulation
antimicrobial
use,
lack
alternatives
ineffective
antimicrobials.
The
plan
strategy
prevention
combating
adopted
countries,
but
fewer
are
able
fully
implement
country-specific
plans,
several
challenges
exist
many
settings.A
concerted
One
Health
approach
will
be
required
ramp
up
region.
addition
surveillance,
effective
infection
control,
water,
sanitation,
hygiene,
stewardship
programs
key
cost-effective
strategies
helping
tackle
AMR.
Philosophical Transactions of the Royal Society B Biological Sciences,
Journal Year:
2022,
Volume and Issue:
377(1861)
Published: Aug. 22, 2022
Horizontal
gene
transfer
(HGT)
drives
microbial
adaptation
but
is
often
under
the
control
of
mobile
genetic
elements
(MGEs)
whose
interests
are
not
necessarily
aligned
with
those
their
hosts.
In
general,
costly
to
donor
cell
while
potentially
beneficial
recipients.
The
diversity
and
plasticity
cell-MGEs
interactions,
among
MGEs,
result
in
complex
evolutionary
processes
where
source,
or
even
existence
selection
for
maintaining
a
function
genome,
unclear.
For
example,
MGE-driven
HGT
depends
on
envelope
structures
defense
systems,
many
these
transferred
by
MGEs
themselves.
can
spur
periods
intense
increasing
own
rates
horizontal
transmission
upon
communicating,
eavesdropping,
sensing
environment
host
physiology.
This
may
high-frequency
genes
unrelated
MGE.
Here,
we
review
how
drive
mechanisms,
selective
pressures
genomic
traits
affect
flow,
therefore
adaptation,
populations.
encoding
adaptive
niche-defining
means
that
intragenomic
conflicts
alliances
between
cells
key
functional
diversification.
article
part
discussion
meeting
issue
'Genomic
population
pathogens'.
Nature Microbiology,
Journal Year:
2022,
Volume and Issue:
7(12), P. 2054 - 2067
Published: Nov. 21, 2022
Abstract
The
Klebsiella
group,
found
in
humans,
livestock,
plants,
soil,
water
and
wild
animals,
is
genetically
ecologically
diverse.
Many
species
are
opportunistic
pathogens
can
harbour
diverse
classes
of
antimicrobial
resistance
genes.
Healthcare-associated
pneumoniae
clones
that
non-susceptible
to
carbapenems
spread
rapidly,
representing
a
high
public
health
burden.
Here
we
report
an
analysis
3,482
genome
sequences
15
sampled
over
17-month
period
from
wide
range
clinical,
community,
animal
environmental
settings
around
the
Italian
city
Pavia.
Northern
Italy
hotspot
for
hospital-acquired
carbapenem
thus
pertinent
setting
examine
overlap
between
isolates
clinical
non-clinical
settings.
We
no
genotypic
or
phenotypic
evidence
non-susceptibility
outside
environment.
Although
noted
occasional
transmission
settings,
our
data
point
limited
role
reservoirs
human
acquisition
spp.
also
provide
detailed
genus-wide
view
genomic
diversity
population
structure,
including
identification
new
groups.
Antibiotics,
Journal Year:
2023,
Volume and Issue:
12(11), P. 1590 - 1590
Published: Nov. 3, 2023
Multidrug-resistant
Gram-negative
bacterial
infections
are
exponentially
increasing,
posing
one
of
the
most
urgent
global
healthcare
and
economic
threats.
Due
to
lack
new
therapies,
World
Health
Organization
classified
these
species
as
priority
pathogens
in
2017,
known
ESKAPE
pathogens.
This
classification
emphasizes
need
for
research
development
novel
targeted
therapies.
The
majority
species,
which
possess
a
structurally
dynamic
cell
envelope
enabling
them
resist
multiple
antibiotics,
thereby
leading
increased
mortality
rates.
Despite
6
years
having
passed
since
WHO
classification,
progress
generating
treatment
ideas
has
not
been
sufficient,
antimicrobial
resistance
continues
escalate,
acting
ticking
time
bomb.
Numerous
efforts
strategies
have
employed
combat
rising
levels
antibiotic
by
targeting
specific
mechanisms.
These
mechanisms
include
inactivating/modifying
enzymes,
outer
membrane
porin
remodelling,
enhanced
efflux
pump
action,
alteration
target
sites.
Some
demonstrated
clinical
promise,
such
utilization
beta-lactamase
inhibitors
adjuvants,
well
recent
advancements
machine-based
learning
employing
artificial
intelligence
facilitate
production
narrow-spectrum
antibiotics.
However,
further
into
an
understanding
precise
occurs,
specifically
tailored
each
could
pave
way
exploring
review
aims
introduce
key
features
bacteria
their
current
approaches,
summarizing
major
with
focus
on
Escherichia
coli,
Acinetobacter
baumannii,
Pseudomonas
aeruginosa,
Klebsiella
pneumoniae.
Additionally,
potential
directions
alternative
therapies
will
be
discussed,
along
relative
modes
providing
future
perspective
insight
discipline
resistance.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Nov. 10, 2022
Abstract
Systemic
characterisation
of
the
human
faecal
microbiome
provides
opportunity
to
develop
non-invasive
approaches
in
diagnosis
a
major
disease.
However,
shared
microbial
signatures
across
different
diseases
make
accurate
challenging
single-disease
models.
Herein,
we
present
machine-learning
multi-class
model
using
metagenomic
dataset
2,320
individuals
with
nine
well-characterised
phenotypes,
including
colorectal
cancer,
adenomas,
Crohn’s
disease,
ulcerative
colitis,
irritable
bowel
syndrome,
obesity,
cardiovascular
post-acute
COVID-19
syndrome
and
healthy
individuals.
Our
processed
data
covers
325
species
derived
from
14.3
terabytes
sequence.
The
trained
achieves
an
area
under
receiver
operating
characteristic
curve
(AUROC)
0.90
0.99
(Interquartile
range,
IQR,
0.91–0.94)
predicting
independent
test
set,
sensitivity
0.81
0.95
(IQR,
0.87–0.93)
at
specificity
0.76
0.98
(IQR
0.83–0.95).
Metagenomic
analysis
public
datasets
1,597
samples
populations
observes
comparable
predictions
AUROC
0.69
0.91
0.79–0.87).
Correlation
top
50
disease
phenotypes
identifies
363
significant
associations
(FDR
<
0.05).
This
microbiome-based
multi-disease
has
potential
clinical
application
diagnostics
treatment
response
monitoring
warrants
further
exploration.
Science Bulletin,
Journal Year:
2023,
Volume and Issue:
68(21), P. 2658 - 2670
Published: Sept. 30, 2023
Although
hypervirulent
Klebsiella
pneumoniae
(hvKP)
can
produce
community-acquired
infections
that
are
fatal
in
young
and
adult
hosts,
such
as
pyogenic
liver
abscess,
endophthalmitis,
meningitis,
it
has
historically
been
susceptible
to
antibiotics.
Carbapenem-resistant
K.
(CRKP)
is
usually
associated
with
urinary
tract
acquired
hospitals,
pneumonia,
septicemias,
soft
tissue
infections.
Outbreaks
quick
spread
of
CRKP
hospitals
have
become
a
major
challenge
public
health
due
the
lack
effective
antibacterial
treatments.
In
early
stages
development,
HvKP
first
appear
distinct
routes.
However,
lines
dividing
two
pathotypes
vanishing
currently,
advent
carbapenem-resistant
(CR-hvKP)
devastating
simultaneously
multidrug-resistant,
hypervirulent,
highly
transmissible.
Most
CR-hvKP
cases
reported
Asian
clinical
settings,
particularly
China.
Typically,
develops
when
hvKP
or
acquires
plasmids
carry
either
carbapenem-resistance
gene
virulence
gene.
Alternatively,
classic
(cKP)
may
acquire
hybrid
plasmid
carrying
both
genes.
this
review,
we
provide
an
overview
key
antimicrobial
resistance
mechanisms,
factors,
presentations,
outcomes
infection.
Additionally,
discuss
possible
evolutionary
processes
prevalence
Given
wide
occurrence
CR-hvKP,
continued
surveillance
control
measures
organisms
should
be
assigned
higher
priority.