The
carbapenem
class
of
antibiotics
is
invaluable
for
the
treatment
selected
multidrug-resistant
Gram-negative
pathogens.
continued
transmission
carbapenem-resistant
bacteria
such
as
ST258
K.
pneumoniae
serious
global
public
health
concern,
options
these
infections
are
limited.
This
genomic
epidemiologic
investigation
traced
natural
history
in
a
single
care
setting
over
nearly
decade.
We
found
that
distinct
subpopulations
have
caused
both
device-associated
and
ward-associated
outbreaks,
some
populations
remain
endemic
within
our
hospital
to
present
day.
finding
virulence
determinants
among
emergent
clones
supports
idea
convergent
evolution
drug-resistant
virulent
CRKP
strains
highlights
need
surveillance,
prevention,
control
efforts
address
evolving
setting.
Clinical Microbiology Reviews,
Год журнала:
2019,
Номер
32(3)
Опубликована: Май 23, 2019
Hypervirulent
K.
pneumoniae
(hvKp)
is
an
evolving
pathotype
that
more
virulent
than
classical
(cKp).
hvKp
usually
infects
individuals
from
the
community,
who
are
often
healthy.
Infections
common
in
Asian
Pacific
Rim
but
occurring
globally.
infection
frequently
presents
at
multiple
sites
or
subsequently
metastatically
spreads,
requiring
source
control.
has
increased
ability
to
cause
central
nervous
system
and
endophthalmitis,
which
require
rapid
recognition
site-specific
treatment.
The
genetic
factors
confer
hvKp's
hypervirulent
phenotype
present
on
a
large
virulence
plasmid
perhaps
integrative
conjugal
elements.
Increased
capsule
production
aerobactin
established
hvKp-specific
factors.
Similar
cKp,
strains
becoming
increasingly
resistant
antimicrobials
via
acquisition
of
mobile
elements
carrying
resistance
determinants,
new
emerge
when
extensively
drug-resistant
cKp
acquire
resulting
nosocomial
infection.
Presently,
clinical
laboratories
unable
differentiate
hvKp,
recently,
several
biomarkers
quantitative
siderophore
have
been
shown
accurately
predict
strains,
could
lead
development
diagnostic
test
for
use
by
optimal
patient
care
epidemiologic
surveillance
research
studies.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Июль 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.
Journal of Internal Medicine,
Год журнала:
2019,
Номер
287(3), С. 283 - 300
Опубликована: Ноя. 2, 2019
Hypervirulent
Klebsiella
pneumoniae
(hvKp)
has
emerged
as
a
concerning
global
pathogen.
hvKp
is
more
virulent
than
classical
K.
(cKp)
and
capable
of
causing
community-acquired
infections,
often
in
healthy
individuals.
carried
the
gastrointestinal
tract,
which
contributes
to
its
spread
community
healthcare
settings.
First
recognized
Asia,
arose
leading
cause
pyogenic
liver
abscesses.
In
decades
since,
globally
causes
variety
infections.
addition
abscesses,
distinct
from
cKp
ability
metastasize
distant
sites,
including
most
commonly
eye,
lung
central
nervous
system
(CNS).
also
been
implicated
primary
extrahepatic
infections
bacteremia,
pneumonia
soft
tissue
The
genetic
determinants
hypervirulence
are
found
on
large
virulence
plasmids
well
chromosomal
mobile
elements
can
be
used
biomarkers
distinguish
clinical
isolates.
These
include
up
four
siderophore
systems
for
iron
acquisition,
increased
capsule
production,
K1
K2
types,
colibactin
toxin.
Additionally,
strains
demonstrate
hypermucoviscosity,
phenotypic
description
laboratory
conditions
that
become
distinguishing
feature
many
hypervirulent
Alarmingly,
multidrug-resistant
have
emerged,
creating
new
challenge
combating
this
already
dangerous
FEMS Microbiology Reviews,
Год журнала:
2018,
Номер
43(2), С. 123 - 144
Опубликована: Ноя. 17, 2018
Klebsiella
species
cause
a
wide
range
of
diseases
including
pneumonia,
urinary
tract
infections
(UTIs),
bloodstream
and
sepsis.
These
are
particularly
problem
among
neonates,
elderly
immunocompromised
individuals.
is
also
responsible
for
significant
number
community-acquired
infections.
A
defining
feature
these
their
morbidity
mortality,
the
strains
associated
with
them
considered
hypervirulent.
The
increasing
isolation
multidrug-resistant
has
significantly
narrowed,
or
in
some
settings
completely
removed,
therapeutic
options
treatment
Not
surprisingly,
this
pathogen
then
been
singled
out
as
an
'urgent
threat
to
human
health'
by
several
organisations.
This
review
summarises
tremendous
progress
that
made
uncover
sophisticated
immune
evasion
strategies
K.
pneumoniae.
co-evolution
response
challenge
activated
formidable
exploiting
stealth
actively
suppressing
innate
defences
overcome
host
responses
survive
tissues.
better
understanding
context
host-pathogen
interactions
pivotal
develop
new
therapeutics,
which
can
be
based
on
antagonising
anti-immune
pathogen.
PLoS Genetics,
Год журнала:
2019,
Номер
15(4), С. e1008114 - e1008114
Опубликована: Апрель 15, 2019
Klebsiella
pneumoniae
has
emerged
as
an
important
cause
of
two
distinct
public
health
threats:
multi-drug
resistant
(MDR)
healthcare-associated
infections
and
drug
susceptible
community-acquired
invasive
infections.
These
pathotypes
are
generally
associated
with
subsets
K.
lineages
or
'clones'
that
distinguished
by
the
presence
acquired
resistance
genes
several
key
virulence
loci.
Genomic
evolutionary
analyses
most
notorious
MDR
community-associated
('hypervirulent')
clones
indicate
differences
in
terms
chromosomal
recombination
dynamics
capsule
polysaccharide
diversity,
but
it
remains
unclear
if
these
represent
generalised
trends.
Here
we
leverage
a
collection
>2200
genomes
to
identify
28
common
(n
≥
10
each),
perform
first
genomic
comparison.
Eight
6
hypervirulent
were
identified
on
basis
gene
prevalence.
Chromosomal
recombination,
surface
locus
pan-genome,
plasmid
phage
characterised
compared.
The
data
showed
highly
diverse,
frequent
generating
extensive
diversity.
Additional
pan-genome
diversity
was
driven
acquisition/loss
both
plasmids
phage.
In
contrast,
rare
clones,
which
also
significant
reduction
largely
Hence
may
be
subject
some
sort
constraint
for
horizontal
transfer
does
not
apply
clones.
Our
findings
relevant
understanding
risk
emergence
individual
strains
carrying
genes,
have
been
increasingly
reported
virulent
extremely
difficult
treat.
Specifically,
our
pose
greatest
risk,
because
they
more
likely
acquire
than
genes.
Nature Microbiology,
Год журнала:
2021,
Номер
6(4), С. 512 - 523
Опубликована: Март 29, 2021
Antimicrobial
resistance
in
neonatal
sepsis
is
rising,
yet
mechanisms
of
that
often
spread
between
species
via
mobile
genetic
elements,
ultimately
limiting
treatments
low-
and
middle-income
countries
(LMICs),
are
poorly
characterized.
The
Burden
Antibiotic
Resistance
Neonates
from
Developing
Societies
(BARNARDS)
network
was
initiated
to
characterize
the
cause
burden
antimicrobial
for
seven
LMICs
Africa
South
Asia.
A
total
36,285
neonates
were
enrolled
BARNARDS
study
November
2015
December
2017,
whom
2,483
diagnosed
with
culture-confirmed
sepsis.
Klebsiella
pneumoniae
(n
=
258)
main
sepsis,
Serratia
marcescens
151),
michiganensis
117),
Escherichia
coli
75)
Enterobacter
cloacae
complex
57)
also
detected.
We
present
whole-genome
sequencing,
susceptibility
clinical
data
916
out
1,038
isolates
(97
not
recovered
initial
isolation
at
local
sites).
Enterobacterales
(K.
pneumoniae,
E.
cloacae)
harboured
multiple
cephalosporin
carbapenem
genes.
All
isolated
pathogens
resistant
antibiotic
classes,
including
those
used
treat
Intraspecies
diversity
K.
indicated
antibiotic-resistant
lineages
Our
results
will
underpin
research
towards
better
LMICs.
Nature Communications,
Год журнала:
2018,
Номер
9(1)
Опубликована: Июль 9, 2018
Severe
liver
abscess
infections
caused
by
hypervirulent
clonal-group
CG23
Klebsiella
pneumoniae
have
been
increasingly
reported
since
the
mid-1980s.
Strains
typically
possess
several
virulence
factors
including
an
integrative,
conjugative
element
ICEKp
encoding
siderophore
yersiniabactin
and
genotoxin
colibactin.
Here
we
investigate
CG23's
evolutionary
history,
showing
deep-branching
sublineages
associated
with
distinct
acquisitions.
Over
80%
of
isolates
belong
to
sublineage
CG23-I,
which
emerged
in
~1928
following
acquisition
ICEKp10
(encoding
colibactin),
then
disseminated
globally
within
human
population.
CG23-I's
distinguishing
feature
is
colibactin
synthesis
locus,
reportedly
promotes
gut
colonisation
metastatic
infection
murine
models.
These
data
show
circulation
K.
decades
before
epidemic
was
first
recognised,
provide
a
framework
for
future
epidemiological
experimental
studies
pneumoniae.
To
support
such
present
open
access,
completely
sequenced
CG23-I
isolate,
SGH10.
Klebsiella
pneumoniae
is
a
leading
cause
of
bloodstream
infection
(BSI).
Strains
producing
extended-spectrum
beta-lactamases
(ESBLs)
or
carbapenemases
are
considered
global
priority
pathogens
for
which
new
treatment
and
prevention
strategies
urgently
required,
due
to
severely
limited
therapeutic
options.
South
Southeast
Asia
major
hubs
antimicrobial-resistant
(AMR)
K.
also
the
characteristically
antimicrobial-sensitive,
community-acquired
"hypervirulent"
strains.
The
emergence
hypervirulent
AMR
strains
lack
data
on
exopolysaccharide
diversity
pose
challenge
BSI
control
worldwide.