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.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: July 7, 2021
Abstract
Klebsiella
pneumoniae
is
a
leading
cause
of
antimicrobial-resistant
(AMR)
healthcare-associated
infections,
neonatal
sepsis
and
community-acquired
liver
abscess,
associated
with
chronic
intestinal
diseases.
Its
diversity
complex
population
structure
pose
challenges
for
analysis
interpretation
K.
genome
data.
Here
we
introduce
Kleborate,
tool
analysing
genomes
its
species
complex,
which
consolidates
interrogation
key
features
proven
clinical
importance.
Kleborate
provides
framework
to
support
genomic
surveillance
epidemiology
in
research,
public
health
settings.
To
demonstrate
utility
apply
analyse
publicly
available
genomes,
including
isolates
from
pan-European
study
carbapenemase-producing
,
highlighting
global
trends
AMR
virulence
as
examples
what
could
be
achieved
by
applying
this
within
more
systematic
efforts.
We
also
the
application
detect
type
gut
metagenomes.
Antimicrobial Agents and Chemotherapy,
Journal Year:
2020,
Volume and Issue:
64(10)
Published: Aug. 3, 2020
There
is
an
enormous
global
public
health
burden
due
to
antimicrobial-resistant
(AMR)
Klebsiella
pneumoniae
high-risk
clones.
K.
ST307
and
ST147
are
recent
additions
the
family
of
successful
clones
in
species.
Both
likely
emerged
Europe
during
early
mid-1990s
and,
a
relatively
short
time,
became
prominent
pathogens,
spreading
all
continents
(with
exception
Antarctica).
consist
multiple
clades/clusters
associated
with
various
carbapenemases
(i.e.,
KPCs,
NDMs,
OXA-48-like,
VIMs).
endemic
Italy,
Colombia,
United
States
(Texas),
South
Africa,
while
India,
Greece,
certain
North
African
countries.
have
been
introduced
into
regions
nonendemicity,
leading
worldwide
nosocomial
outbreaks.
Genomic
studies
showed
contain
identical
gyrA
parC
mutations
obtained
plasmids
blaCTX-M-15
mid-2000s,
which
aided
their
distribution.
then
acquired
late
2000s,
establishing
themselves
as
important
AMR
pathogens
regions.
underreported
restricted
detection
methodologies.
ability
become
major
threats
distribution,
cause
serious
infections,
association
AMR,
including
panresistance.
The
medical
community
at
large,
especially
those
concerned
antimicrobial
resistance,
should
be
aware
looming
threat
posed
by
emerging
such
ST147.
Frontiers in Microbiology,
Journal Year:
2021,
Volume and Issue:
12
Published: April 8, 2021
Hypervirulent
Klebsiella
pneumoniae
(hvKP)
has
spread
globally
since
first
described
in
the
Asian
Pacific
Rim.
It
is
an
invasive
variant
that
differs
from
classical
K.
(cKP),
with
hypermucoviscosity
and
hypervirulence,
causing
community-acquired
infections,
including
pyogenic
liver
abscess,
pneumonia,
meningitis,
endophthalmitis.
utilizes
a
battery
of
virulence
factors
for
survival
pathogenesis,
such
as
capsule,
siderophores,
lipopolysaccharide,
fimbriae,
outer
membrane
proteins,
type
6
secretion
system,
which
former
two
are
dominant.
This
review
summarizes
these
hvKP-associated
order
to
understand
its
molecular
pathogenesis
shed
light
on
new
strategies
improve
prevention,
diagnosis,
treatment
hvKP-causing
infection.
Journal of Global Antimicrobial Resistance,
Journal Year:
2021,
Volume and Issue:
25, P. 26 - 34
Published: March 2, 2021
Hypervirulence
and
carbapenem
resistance
have
emerged
as
two
distinct
evolutionary
directions
for
Klebsiella
pneumoniae,
which
pose
a
great
threat
in
clinical
settings.
Multiple
virulence
factors
contribute
to
hypervirulence,
the
mechanisms
of
are
complicated.
However,
more
K.
pneumoniae
strains
been
identified
recent
years
integrating
both
phenotypes,
resulting
devastating
outcomes.
Hypervirulent
carbapenem-resistant
(CR-hvKP)
early
2010s
thereafter
become
increasingly
prevalent.
CR-hvKP
primarily
prevalent
Asia,
especially
China,
but
reported
all
over
world.
Mechanisms
emergence
can
be
summarised
by
three
patterns:
(i)
(CRKP)
acquiring
hypervirulent
phenotype;
(ii)
(hvKP)
(iii)
hypervirulence
hybrid
plasmid.
With
their
global
dissemination,
continued
surveillance
should
highly
prioritised.
EBioMedicine,
Journal Year:
2022,
Volume and Issue:
79, P. 103998 - 103998
Published: April 8, 2022
Members
of
the
genus
Klebsiella
have
rapidly
evolved
within
past
decade,
generating
organisms
that
simultaneously
exhibit
both
multidrug
resistance
and
hypervirulence
(MDR-hv)
phenotypes;
such
are
associated
with
severe
hospital-
community-acquired
infections.
Carbapenem-resistant
infections
unknown
optimal
treatment
regime
were
particular
concern
among
MDR-hv
strains.
Recent
studies
revealed
molecular
features
mobile
elements
they
harbour,
allowing
identification
genetic
loci
responsible
for
transmission,
stable
inheritance,
expression
or
virulence-encoding
confer
new
phenotypic
characteristics
spp.
Here,
we
provide
a
comprehensive
review
on
taxonomic
position,
species
composition
different
phylotypes
spp.,
describing
diversity
worldwide
distribution
clones,
mutation
horizontal
gene
transfer
events
drive
evolution
potential
impact
human
health.
Microbial Genomics,
Journal Year:
2022,
Volume and Issue:
8(3)
Published: March 1, 2022
The
outer
polysaccharide
capsule
and
lipopolysaccharide
(LPS)
antigens
are
key
targets
for
novel
control
strategies
targeting
Klebsiella
pneumoniae
related
taxa
from
the
K.
species
complex
(KpSC),
including
vaccines,
phage
monoclonal
antibody
therapies.
Given
importance
growing
interest
in
these
highly
diverse
surface
antigens,
we
had
previously
developed
Kaptive,
a
tool
rapidly
identifying
typing
(K)
LPS
(O)
loci
whole
genome
sequence
data.
Here,
report
two
significant
updates,
now
freely
available
Kaptive
2.0
(
https://github.com/katholt/kaptive
):
(i)
addition
of
16
K
locus
sequences
to
reference
database
following
an
extensive
search
>17
000
KpSC
genomes;
(ii)
enhanced
O
enable
prediction
clinically
relevant
O2
antigen
(sub)types,
which
genetic
determinants
have
been
recently
described.
We
applied
curated
dataset
>12
public
genomes
explore
first
time,
best
our
knowledge,
distribution
predicted
(sub)types
across
species,
sampling
niches
clones,
highlighted
differences
distributions
that
warrant
further
investigation.
As
uptake
genomic
surveillance
approaches
continues
expand
globally,
application
will
generate
insights
essential
design
effective
strategies.
Antibiotics,
Journal Year:
2023,
Volume and Issue:
12(2), P. 234 - 234
Published: Jan. 21, 2023
Klebsiella
pneumoniae
is
a
Gram-negative
opportunistic
pathogen
responsible
for
variety
of
community
and
hospital
infections.
Infections
caused
by
carbapenem-resistant
K.
(CRKP)
constitute
major
threat
public
health
are
strongly
associated
with
high
rates
mortality,
especially
in
immunocompromised
critically
ill
patients.
Adhesive
fimbriae,
capsule,
lipopolysaccharide
(LPS),
siderophores
or
iron
carriers
the
main
virulence
factors
which
contribute
to
pathogenicity
pneumoniae.
Colistin
tigecycline
some
last
resorts
treatment
CRKP
Carbapenemase
production,
carbapenemase
(KPC)
metallo-β-lactamase
(MBL),
constitutes
basic
molecular
mechanism
emergence.
Knowledge
appearance
crucial,
as
it
can
determine
selection
most
suitable
antimicrobial
agent
among
those
recently
launched.
Plazomicin,
eravacycline,
cefiderocol,
temocillin,
ceftolozane–tazobactam,
imipenem–cilastatin/relebactam,
meropenem–vaborbactam,
ceftazidime–avibactam
aztreonam–avibactam
potent
alternatives
treating
The
aim
current
review
highlight
pathogenesis
provide
recent
updates
on
epidemiology
options.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: May 31, 2022
Abstract
Klebsiella
pneumoniae
is
a
major
cause
of
opportunistic
healthcare-associated
infections,
which
are
increasingly
complicated
by
the
presence
extended-spectrum
beta-lactamases
(ESBLs)
and
carbapenem
resistance.
We
conducted
year-long
prospective
surveillance
study
K.
clinical
isolates
in
hospital
patients.
Whole-genome
sequence
(WGS)
data
reveals
diverse
pathogen
population,
including
other
species
within
complex
(18%).
Several
infections
were
caused
variicola/K.
hybrids,
one
shows
evidence
nosocomial
transmission.
A
wide
range
antimicrobial
resistance
(AMR)
phenotypes
observed,
genetic
mechanisms
identified
(mainly
plasmid-borne
genes).
ESBLs
correlated
with
acquired
AMR
genes
(median
n
=
10).
Bacterial
genomic
features
associated
onset
(OR
2.34,
p
0.015)
rhamnose-positive
capsules
3.12,
<
0.001).
Virulence
plasmid-encoded
(aerobactin,
hypermucoidy)
observed
at
low-prevalence
(<3%),
mostly
community-onset
cases.
WGS-confirmed
transmission
implicated
just
10%
cases,
but
strongly
21,
1
×
10
−11
).
estimate
28%
risk
onward
for
ESBL-positive
strains
vs
1.7%
ESBL-negative
strains.
These
indicate
that
hospitalised
patients
due
largely
to
strains,
an
additional
burden
from
nosocomially-transmitted
community-acquired
hypervirulent