Rapid emergence, transmission, and evolution of KPC and NDM coproducing carbapenem-resistant Klebsiella pneumoniae
Microbiological Research,
Год журнала:
2025,
Номер
293, С. 128049 - 128049
Опубликована: Янв. 5, 2025
Язык: Английский
Enhanced invasion and survival of antibiotic- resistant Klebsiella pneumoniae pathotypes in host cells and strain-specific replication in blood
Frontiers in Cellular and Infection Microbiology,
Год журнала:
2025,
Номер
15
Опубликована: Фев. 14, 2025
Background
Klebsiella
pneumoniae
is
one
of
the
most
important
opportunistic
pathogens
causing
healthcare-associated
and
community-acquired
infections
worldwide.
In
recent
years,
increase
in
antibiotic
resistance
caused
by
hypervirulent
K.
poses
great
public
health
concerns.
this
study,
host-pathogen
interactions
different
strains
human
animal
origins
were
analyzed
microbiological,
cell-biological
immunological
experiments.
Methods
vitro
infection
experiments
using
representatives
pathotypes
various
epithelial
macrophage
cell
lines
executed
analyzing
adhesion,
invasion
intracellular
replication.
Experimental
conditions
involved
normoxia
hypoxia.
Furthermore,
survival
growth
further
isolates
expressing
defined
siderophores
blood
(platelet
concentrates,
serum)
was
investigated.
All
done
triplicate
statistically
significant
differences
determined.
Results
Significant
adhesion
capability,
phagocytosis
replication
measured
between
pathotypes.
Especially,
ESBL-producing
demonstrated
increased
host
macrophages.
A
strong
cytotoxic
effect
on
intestinal
cells
observed
for
.
The
results
from
our
investigations
behavior
platelets
serum
showed
that
and/or
an
enlarged
capsule
are
not
essential
factors
proliferation
(hypervirulent)
components.
Conclusion
Our
revealed
new
insights
into
representing
pathovars
clonal
lineages
infectious
contexts
hosts.
While
a
clear
limitation
study
limited
strain
set
used
both
as
potential
host,
step
better
understanding
pathogenicity
its
properties
stages
colonization
infection.
When
developed
further,
these
may
offer
novel
approaches
future
therapeutics
including
“anti-virulence
strategies”.
Язык: Английский
Type I-E* CRISPR-Cas of Klebsiella pneumoniae upregulates bacterial virulence by targeting endogenous histidine utilization system
mSphere,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 19, 2025
ABSTRACT
Klebsiella
pneumoniae
is
a
globally
recognized
microbial
pathogen
with
significant
clinical
impact.
The
bacterium
harbors
the
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)-Cas
systems,
which
provide
adaptive
immunity
against
invading
foreign
nucleic
acids.
Recent
studies
suggest
that
certain
CRISPR-Cas
systems
can
regulate
endogenous
genes,
influencing
bacterial
virulence.
However,
their
role
in
regulating
pathogenicity
K.
remains
poorly
understood.
This
study
investigates
regulatory
of
type
I-E*
system
hypervirulent
strain,
focusing
on
its
impact
histidine
metabolism
and
pathogenicity.
Transcriptome
analyses
identified
differentially
expressed
genes
(DEGs)
between
casABECD
-deletion
wild-type
strains,
including
upregulation
utilization
(Hut)
operon
downregulation
biofilm-related
genes.
These
molecular
changes
resulted
enhanced
metabolic
activity,
reduced
biofilm
formation,
attenuated
virulence
A549
lung
epithelial
cells,
improved
survival
Galleria
mellonella
,
as
validated
through
phenotypic
assays.
Our
bioinformatic
analysis
indicated
targets
hutT
sequence,
part
Hut
operon.
Furthermore,
overexpression
mitigated
CRISPR-Cas-mediated
repression
operon,
observed
assays,
while
simultaneous
deletion
hutH
restored
Δ
strain.
Additionally,
significantly
enhances
growth
strain
medium
sole
carbon
source,
highlighting
intricate
adaptation.
Collectively,
these
findings
uncover
novel
for
pathways
.
IMPORTANCE
Clustered
are
primarily
roles
genetic
elements
bacteria.
emerging
evidence
indicates
also
thereby
physiology
In
this
study,
we
demonstrate
gene,
critical
component
pathway.
targeting
potentially
impacts
transcription
alters
expression
other
hut
ultimately
enhancing
reveal
previously
unrecognized
mechanism
facilitate
adaptation
broadens
our
understanding
multifaceted
pathobiology,
implications
clinically
relevant
pathogens.
Язык: Английский
The Challenge of Treating Infections Caused by Metallo‐β‐Lactamase–Producing Gram-Negative Bacteria: A Narrative Review
Drugs,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 28, 2024
Gram-negative
multidrug-resistant
(MDR)
bacteria,
including
Enterobacterales,
Acinetobacter
baumannii,
and
Pseudomonas
aeruginosa,
pose
a
significant
challenge
in
clinical
practice.
Infections
caused
by
metallo-β-lactamase
(MBL)–producing
organisms,
particular,
require
careful
consideration
due
to
their
complexity
varied
prevalence,
given
that
the
microbiological
diagnosis
of
these
pathogens
is
intricate
compounded
challenges
assessing
efficacy
anti-MBL
antimicrobials.
We
discuss
both
established
new
approaches
treatment
MBL–producing
infections,
focusing
on
3
strategies:
colistin;
recently
approved
combination
aztreonam
with
avibactam
(or
ceftazidime/avibactam);
cefiderocol.
Despite
its
activity
against
various
pathogens,
colistin
limited
resistance
mechanisms,
while
nephrotoxicity
acute
renal
injury
call
for
dosing
monitoring
Aztreonam
combined
avibactam/ceftazidime
if
plus
not
available)
exhibits
potent
pathogens.
Cefiderocol
monotherapy
effective
wide
range
MBL
producers,
favorable
outcomes
have
been
observed
trials
case
series.
After
examining
scientific
evidence
management
infections
we
developed
comprehensive
algorithm
guide
therapeutic
decision
making.
recommend
reserving
as
last-resort
option
MDR
infections.
aztreonam/avibactam
represent
options
In
P.
aeruginosa
enzymes
difficult-to-treat
resistance,
cefiderocol
preferred
option.
Further
research
needed
optimize
strategies
minimize
resistance.
Язык: Английский
Contributions of Long-Read Sequencing for the Detection of Antimicrobial Resistance
Pathogens,
Год журнала:
2024,
Номер
13(9), С. 730 - 730
Опубликована: Авг. 28, 2024
Background.
In
the
context
of
increasing
antimicrobial
resistance
(AMR),
whole-genome
sequencing
(WGS)
bacteria
is
considered
a
highly
accurate
and
comprehensive
surveillance
method
for
detecting
tracking
spread
resistant
pathogens.
Two
primary
technologies
exist:
short-read
(50–300
base
pairs)
long-read
(thousands
pairs).
The
former,
based
on
Illumina
platforms
(ISPs),
provides
extensive
coverage
high
accuracy
single
nucleotide
polymorphisms
(SNPs)
small
insertions/deletions,
but
limited
by
its
read
length.
latter,
such
as
Oxford
Nanopore
Technologies
(ONT),
enables
assembly
genomes,
particularly
those
with
repetitive
regions
structural
variants,
although
has
historically
been
lower.
Results.
We
performed
head-to-head
comparison
these
techniques
to
sequence
K.
pneumoniae
VS17
isolate,
focusing
blaNDM
gene
alleles
in
program.
Discrepancies
between
ISP
(blaNDM-4
allele
identified)
ONT
(blaNDM-1
blaNDM-5
were
observed.
Conjugation
assays
Sanger
sequencing,
used
gold
standard,
confirmed
validity
results.
This
study
demonstrates
importance
or
hybrid
assemblies
carbapenemase
identification
highlights
limitations
short
reads
duplications
multiple
alleles.
Conclusions.
this
proof-of-concept
study,
we
conclude
that
recent
technology
may
outperform
standard
Such
information
crucial
given
rising
prevalence
strains
producing
carbapenemases,
especially
WGS
increasingly
epidemiological
infection
control.
Язык: Английский
Case report of cefiderocol-resistant hypervirulent Klebsiella pneumoniae with CirA deficiency and co-production of KPC-2 and SHV-12
Clinical Microbiology and Infection,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 1, 2024
Язык: Английский
Multispecies emergence of dual bla KPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile
Antimicrobial Agents and Chemotherapy,
Год журнала:
2024,
Номер
69(1)
Опубликована: Дек. 5, 2024
Carbapenemase-producing
carbapenem-resistant
Enterobacterales
(CP-CRE)
represent
a
significant
global
threat.
The
emergence
of
dual
CP-CRE
is
particularly
alarming,
as
they
can
potentially
compromise
the
efficacy
newer
antibiotics,
further
decreasing
therapeutic
alternatives.
Herein,
we
report
multiple
species
recovered
from
invasive
infections
in
Chile
that
simultaneously
harbor
blaKPC
and
blaNDM
provide
an
in-depth
genomic
characterization
these
worrisome
pathogens.
We
collected
(CRE)
isolates
over
4-year
period,
across
11
healthcare
centers
Chile.
Bacterial
presence
carbapenemase
genes
were
confirmed
using
MALDI-TOF
PCR
assays,
respectively.
Antimicrobial
susceptibility
testing
was
conducted
through
disk
diffusion
broth
microdilution
methods.
Dual
subjected
to
short-
long-read
whole
genome
sequencing
perform
detailed
mobile
genetic
elements
harboring
enzymes.
From
total
1,335
CRE
isolates,
observed
increase
prevalence
CP-CRE,
11%
2019
38%
2022.
A
recovered,
all
them
blaNDM.
Species
corresponded
Escherichia
coli
(n
=
6),
Klebsiella
pneumoniae
2),
oxytoca
Citrobacter
freundii
1).
exhibited
resistance
tested
β-lactams
except
for
cefiderocol.
encoding
located
on
independent
plasmids.
Platforms
diverse
included
IncN,
IncF,
IncFIB
In
contrast,
blaNDM-7
only
found
fairly
conserved
IncX3
rapid
Chile,
alongside
with
bacterial
co-harboring
blaKPC-2/3
blaNDM-7,
underscores
critical
public
health
challenge.
Our
data
suggest
dissemination
predominantly
facilitated
by
plasmids,
whereas
spread
involved
plasmid
backbones.
Active
surveillance
monitoring
are
inform
policy
curtail
highly
resistant
Язык: Английский