Molecular epidemiology and β-lactam resistance mechanisms of Enterobacter cloacae complex isolates obtained from bloodstream infections, Kyoto, Japan
Microbiology Spectrum,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 10, 2025
ABSTRACT
The
Enterobacter
cloacae
complex
(ECC)
comprises
multiple
species
that
require
genomic
analysis
for
precise
identification.
They
produce
inducible
AmpC
β-lactamase
and
may
carry
acquired
β-lactamases,
which
are
responsible
cefotaxime
cefepime
resistance.
To
determine
the
molecular
epidemiology,
antimicrobial
resistance,
β-lactam
resistance
mechanisms
of
ECC,
we
conducted
whole-genome
sequencing
analysis,
susceptibility
testing,
mutation
on
bloodstream
ECC
isolates
from
patients
in
Kyoto,
Japan.
In
194
isolates,
13
six
unnamed
taxa
were
identified,
with
xiangfangensis
(36%)
being
most
common.
A
total
38%
nonsusceptible
to
presented
relatively
high
nonsusceptibility
rates
all
agents
tested.
Among
different
species,
hoffmannii
highest
both
β-lactams
non-β-lactams.
cefotaxime-nonsusceptible
16%
harbored
genes
encoding
extended-spectrum
β-lactamases
(ESBLs),
carbapenemase,
and/or
plasmid-mediated
AmpC,
ampC
derepression
was
predominant
mechanism
remaining
isolates.
prevalent
sequence
types
(STs)
cefotaxime-susceptible
different,
although
some
STs
shared
by
groups.
Cefepime
detected
7%
associated
E.
ST78
ST93,
ESBLs.
Sixty-four
mutants,
experimentally
obtained
eight
had
various
ampD
mutations,
42%
99%
mutants
piperacillin/tazobactam,
respectively,
indicating
risks
use
these
antimicrobials.
Continuous
surveillance
via
phenotypic
analyses
is
needed
combat
ECC.
IMPORTANCE
a
group
pathogenic
bacteria
cause
nosocomial
infections.
produces
chromosomal
treatment
failure
despite
initial
third-generation
cephalosporins
selected
-derepressed
mutants.
challenges
identification
have
complicated
our
understanding
selection
appropriate
treatment.
this
study,
performed
phenotypic,
sequencing,
among
infections
molecular-based
third-/fourth-generation
cephalosporins,
specific
clones
contribute
acquisition
fourth-generation
cephalosporin
ampC-
derepressed
These
data
will
help
elucidate
local
epidemiology
guide
therapy
infection
control
strategies
ECC-related
Language: Английский
A Review of In Silico and In Vitro Approaches in the Fight Against Carbapenem‐Resistant Enterobacterales
Journal of Clinical Laboratory Analysis,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 9, 2025
ABSTRACT
Objectives
The
rise
in
carbapenem‐resistant
Enterobacterales
(CRE)
has
reinforced
the
global
quest
for
developing
effective
therapeutics.
Traditional
drug
discovery
approaches
have
been
inadequate
overcoming
this
challenge
due
to
their
resource
and
time
constraints.
Methods
English
literature
was
searched
by
structured
queries
related
our
review
between
January
1,
2020,
December
31,
2024.
Results
key
resistance
mechanisms
CRE,
such
as
enzymatic
hydrolysis,
decreased
permeability,
efflux
pump
overexpression,
examined
review.
Computational
technologies
become
pivotal
discovering
novel
antimicrobial
agents
with
improved
accuracy
efficiency.
Besides
this,
highlights
advances
structure‐
ligand‐based
identifying
potential
drugs
against
CRE.
Recent
studies
demonstrating
use
of
silico
techniques
develop
targeted
CRE
also
explored.
Moreover,
underscores
significance
integrating
both
vitro
counter
Enterobacterales,
supported
latest
studies.
However,
these
promising
computational
a
few
major
drawbacks,
lack
standardized
parameterization,
potentially
false
positives,
complexity
clinical
translations.
regulatory
barriers
restrict
progress
new
antimicrobials
market
approval.
Conclusion
inhibitor
is
gaining
popularity,
it
can
be
expedited
refining
them
reliable
validation.
innovative
hybrid
need
hour
tackle
mitigate
threat
resistance.
Language: Английский
Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane
Communications Biology,
Journal Year:
2024,
Volume and Issue:
7(1)
Published: Nov. 14, 2024
The
sophisticated
envelope
of
Gram-negative
bacteria
modulates
the
uptake
small
molecules
in
a
side-chain-sensitive
manner.
Despite
intensive
theoretical
and
experimental
investigations,
general
set
pathways
underpinning
antibiotic
has
not
been
identified.
This
manuscript
discusses
passive
influx
versus
active
efflux
antibiotics,
considering
responsible
membrane
proteins
transported
molecules.
Recent
methods
have
analyzed
drug
transport
across
bacterial
order
to
understand
their
activity.
combination
vitro,
cellulo
silico
shed
light
on
key,
mainly
electrostatic,
interactions
between
molecule
surface,
porins
transporters
during
permeation.
A
key
factor
is
relationship
dose
an
compound
near
its
target
antibacterial
activity
critical
early
window.
Today,
methodology
breakthroughs
provide
fruitful
tools
precisely
dissect
transport,
identify
steps
resistance
associated
with
impermeability
efflux,
highlight
parameters
generate
more
effective
drugs.
controls
accumulation
via
mechanisms.
article
recent
cellulo,
highlighting
"drug-transporters"
dialogues
proposes
new
perspectives
overcome
resistance.
Language: Английский