ABSTRACT
Antimicrobial
resistance
(AMR)
is
a
public
health
threat
worldwide.
Next-generation
sequencing
(NGS)
has
opened
unprecedented
opportunities
to
accelerate
AMR
mechanism
discovery
and
diagnostics.
Here,
we
present
an
integrative
approach
investigate
trimethoprim
(TMP)
in
the
key
pathogen
Streptococcus
pneumoniae
.
We
explored
collection
of
662
S
genomes
by
conducting
genome-wide
association
study
(GWAS),
followed
functional
validation
using
reconstruction
experiments,
combined
with
machine
learning
(ML)
approaches
predict
TMP
minimum
inhibitory
concentration
(MIC).
Our
showed
that
multiple
additive
mutations
folA
sulA
loci
are
responsible
for
non-susceptibility
S.
can
be
used
as
features
build
ML
models
digital
MIC
prediction,
reaching
average
accuracy
within
±1
twofold
dilution
factor
86.3%.
roadmap
silico
analysis—wet-lab
validation—diagnostic
tool
building
could
adapted
explore
other
combinations
bacteria–antibiotic.
IMPORTANCE
In
age
next-generation
(NGS),
while
data-driven
methods
such
(GWAS)
excel
at
finding
patterns,
challenging
due
high
numbers
candidate
variants.
designed
combining
GWAS
on
clinical
isolates,
whole-genome
transformation
coupled
NGS
functionally
characterize
large
set
candidates.
validated
several
phenotypic
beyond
standard
Ile100Leu
mutation,
overexpression
locus
produces
These
loci,
when
models,
were
found
best
inputs
predicting
minimal
concentrations.
Integrative
bridge
genotype-phenotype
gap
biological
insights
incorporated
accurate
prediction
drug
susceptibility.
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
265, С. 131007 - 131007
Опубликована: Март 18, 2024
Derived
from
bountiful
marine
organisms
(predominantly
algae,
fauna,
and
microorganisms),
polysaccharides
oligosaccharides
are
intricate
macromolecules
that
play
a
significant
role
in
the
growth
development
of
life.
Recently,
considerable
attention
has
been
paid
to
as
auspicious
natural
products
due
their
promising
biological
attributes.
Herein,
we
provide
an
overview
recent
advances
miscellaneous
activities
encompasses
anti-cancer,
anti-inflammatory,
antibacterial,
antiviral,
antioxidant,
anti-diabetes
mellitus,
anticoagulant
properties.
Furthermore,
furnish
concise
summary
underlying
mechanisms
governing
behavior
these
macromolecules.
We
hope
this
review
inspires
research
on
medicinal
applications
while
offering
fresh
perspectives
broader
facets.
Frontiers in Microbiology,
Год журнала:
2025,
Номер
16
Опубликована: Янв. 28, 2025
Introduction
The
Streptococcus
pneumoniae
(pneumococcus)
competence
regulon
is
well-known
for
regulating
genetic
transformation
but
also
important
virulence.
Some
pneumococcal
strains
can
enter
a
transient
competent
state
in
an
optimized
competence-inducing
medium
when
the
threshold
level
of
peptide
pheromone
stimulating
attained;
upregulating
expression
three
distinct
phases
“early”,
“late”
and
“delayed”
genes.
Recently,
we
discovered
that
pneumococcus
naturally
prolonged
during
acute
pneumonia
mice.
However,
mechanisms
driving
development
host
infection
are
rarely
examined,
direct
comparison
between
vitro
vivo
induction
has
not
been
performed.
Methods
We
conducted
comparative
gene
analysis
versus
pneumonia-derived
sepsis
examined
existing
RNA-Seq
data
performed
validation
using
RNA
obtained
from
independent
replicate
experiment.
Results
discussion
Our
revealed
both
similarities
differences
“late”,
sepsis.
results
may
reveal
new
aspects
biology.
Ear and Hearing,
Год журнала:
2024,
Номер
45(3), С. 658 - 665
Опубликована: Янв. 5, 2024
Objectives:
Otitis
media
is
one
of
the
most
important
causes
hearing
loss
at
an
early
age.
Effective
vaccination
with
routine
7-valent
pneumococcal
conjugate
vaccine
(PCV-7)
was
introduced
in
2000.
It
has
been
gradually
replaced
by
nontypeable
Haemophilus
influenzae
protein
D
or
higher-valent
13-valent
PCV
(PCV-13)
since
2010.
Data
on
change
otitis
burden
recent
years
are
sparse
global,
regional,
and
national
levels.
Design:
The
Global
Burden
Disease
2019
study
used
to
evaluate
prevalence,
incidence,
mortality,
disability-adjusted
life
year
(DALY)
rates,
average
annual
percentage
changes
(AAPCs)
geographic
populations
worldwide
from
1990
2019.
These
global
trends
were
further
analyzed
subgroup
(age,
sex,
sociodemographic
index
[SDI]).
Results:
Globally,
all-age
rate
prevalence
(AAPC
=
−0.7,
95%
confidence
interval
[CI]
−0.7
−0.8),
DALYs
−1.0,
CI
−1.1
−1.0),
mortality
−6.8,
−7.3
−6.4)
decreased
constantly
between
incidence
sharply
2000
2009
AAPC
−1.2
(95%
−1.4
−0.9)
continued
downward
trend
2010
−0.2,
−0.3
−0.1).
In
2019,
children
aged
1
4
old
had
highest
29,127.3
per
100,000
population,
while
young
adults
under
30
accounted
for
91.3%
incident
cases.
Individuals
living
middle-SDI
countries
largest
increase
media,
0.3
0.3)
increasing
SDI.
Regionally,
observed
high-income
Asia
Pacific,
Eastern
Europe,
Western
Sub-Saharan
Africa
Nationally,
Republic
Korea,
0.8
0.6
1.1)
same
time
period.
Conclusions:
There
have
successful
previous
endeavors
reduce
attributed
a
scale.
experienced
sharp
decline
following
introduction
PCV-7
2000,
this
persisted
subsequent
adoption
PCV-13/pneumococcal
vaccine.
Continual
epidemiological
surveillance
media’s
trends,
pathogen
distribution,
resistance
patterns
remains
imperative.
Medicina,
Год журнала:
2023,
Номер
59(11), С. 1927 - 1927
Опубликована: Окт. 31, 2023
Streptococcus
pneumoniae
(S.
pneumoniae)
is
a
bacterial
species
often
associated
with
the
occurrence
of
community-acquired
pneumonia
(CAP).
CAP
refers
to
specific
kind
that
occurs
in
individuals
who
acquire
infection
outside
healthcare
setting.
It
represents
leading
cause
both
death
and
morbidity
on
global
scale.
Moreover,
declaration
S.
as
one
12
pathogens
was
made
by
World
Health
Organization
(WHO)
2017.
Antibiotics
like
β-lactams,
macrolides,
fluoroquinolones
are
primary
classes
antimicrobial
medicines
used
for
treatment
infections.
Nevertheless,
efficacy
these
antibiotics
diminishing
result
establishment
resistance
against
agents.
In
2019,
WHO
declared
antibiotic
among
top
10
hazards
worldwide
health.
believed
penicillin-binding
protein
genetic
alteration
causes
β-lactam
resistance.
Ribosomal
target
site
alterations
active
efflux
pumps
macrolide
Numerous
factors,
including
accumulation
mutations,
enhanced
mechanisms,
plasmid
gene
acquisition,
fluoroquinolone
Furthermore,
despite
advancements
pneumococcal
vaccinations
artificial
intelligence
(AI),
it
not
feasible
rely
them
indefinitely.
The
ongoing
development
AI
combating
necessitates
more
research
efforts.
A
few
strategies
can
be
performed
curb
this
issue,
providing
educational
initiatives
guidelines,
conducting
surveillance,
establishing
new
targeting
another
part
bacteria.
Hence,
understanding
mechanism
may
aid
researchers
developing
efficacious
future
endeavors.
Frontiers in Microbiology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 1, 2024
Background
Streptococcus
pneumoniae
is
a
common
pathogen
that
colonizes
the
human
upper
respiratory
tract,
causing
high
morbidity
and
mortality
worldwide.
This
study
aimed
to
investigate
prevalence
status
of
S.
isolated
from
patients
all
ages
in
Southwest
China,
including
serotype,
antibiotic
susceptibility
other
molecular
characteristics,
provide
basis
for
clinical
usage
vaccine
development.
Methods
was
conducted
January
2018
March
2022
at
West
China
Hospital,
Second
University
First
People’s
Hospital
Longquanyi
District
(West
Longquan
Hospital),
Meishan
Women
Children’s
(Alliance
Hospital)
Chengdu
Jinjiang
Children
Health.
Demographic
characteristics
263
pneumococcal
disease
(PD)
all-age
were
collected
analyzed.
The
serotypes,
sequence
types
(STs),
resistance
strains
determined
by
next-generation
sequencing,
analysis
microdilution
broth
method.
Results
most
serotypes
19F
(17.87%),
19A
(11.41%),
3
(8.75%),
23F
(6.46%)
6A
(5.70%).
Coverage
rates
PCV10,
PCV13,
PCV15,
PCV20
PCV24
36.12,
61.98,
63.12
64.26%,
respectively.
Prevalent
STs
ST271
(12.55%),
ST320
(11.79%),
ST90
(4.18%),
ST876
(4.18%)
ST11972
(3.42%).
Penicillin-resistant
(PRSP)
accounted
82.35
1.22%
meningitis
nonmeningitis
PD
cases,
Resistance
genes
msrD
(32.7%),
mefA
ermB
(95.8%),
tetM
(97.3%)
catTC
(7.6%)
found
among
isolates.
Most
isolates
showed
erythromycin
(96.96%)
tetracycline
(79.85%),
with
more
than
half
being
resistant
SXT
(58.94%).
A
few
AMX
(9.89%),
CTX
(11.03%),
MEN
(9.13%),
OFX
(1.14%),
LVX
(1.14%)
MXF
(0.38%).
All
susceptible
vancomycin
linezolid.
Conclusion
Our
provides
reliable
information,
prevalence,
characterization
antimicrobial
diseases
China.
findings
contribute
informed
policy
decisions
prevention
treatment.
PLoS ONE,
Год журнала:
2023,
Номер
18(3), С. e0282970 - e0282970
Опубликована: Март 22, 2023
Background
This
systematic
review
evaluates
pneumolysin
(PLY)
as
a
target
for
new
treatments
against
pneumococcal
infections.
Pneumolysin
is
one
of
the
main
virulence
factors
produced
by
all
types
pneumococci.
toxin
(53
kDa)
highly
conserved
protein
that
binds
to
cholesterol
in
eukaryotic
cells,
forming
pores
lead
cell
destruction.
Methods
The
databases
consulted
were
MEDLINE,
Web
Science,
and
Scopus.
Articles
independently
screened
title,
abstract,
full
text
two
researchers,
using
consensus
resolve
any
disagreements
occurred.
other
languages
different
from
English,
patents,
cases
report,
notes,
chapter
books
reviews
excluded.
Searches
restricted
years
2000
2021.
Methodological
quality
was
evaluated
OHAT
framework.
Results
Forty-one
articles
describing
effects
molecules
inhibit
PLY
reviewed.
Briefly,
inhibitory
found
classified
into
three
groups:
those
exerting
direct
effect
binding
and/or
blocking
PLY,
acting
indirectly
preventing
its
on
host
whose
mechanisms
are
unknown.
Although
many
proposed
blockers,
only
some
them,
such
antibiotics,
peptides,
sterols,
statins,
have
probability
being
implemented
clinical
treatment.
In
contrast,
molecules,
there
limited
studies
demonstrate
efficacy
animal
models
with
sufficient
reliability.
Discussion
Most
reviewed
has
good
level
confidence.
However,
limitations
this
lack
homogeneity
studies,
what
prevented
carry
out
statistical
comparison
results
or
meta-analysis.
Conclusion
A
panel
activity
associated
improvement
inflammatory
process
triggered
infection.
Some
already
been
used
humans
purposes,
so
they
could
be
safe
use
patients
These
might
benefit
second
line
treatment
during
initial
stages
infection
acute
respiratory
distress
syndrome
invasive
diseases.
Additional
research
presented
set
compounds
further
improve
management
these
patients.
Heliyon,
Год журнала:
2024,
Номер
10(16), С. e35841 - e35841
Опубликована: Авг. 1, 2024
The
aim
of
this
study
was
to
investigate
the
global
epidemiological
trends
in
incidence
and
deaths
acute
respiratory
infections
(ARIs),
encompassing
both
upper
(URIs)
lower
(LRIs),
from
1990
2021.
Using
data
Global
Burden
Disease
2021
(GBD
2021),
we
utilized
average
annual
percentage
change
(AAPC)
examine
age-standardized
rate
(ASIR
ASDRs)
URIs
LRIs.
In
2021,
ASIR
LRIs
were
166,770.73
(95
%
UI:
148,098.16–189,487.93)
per
100,000
4283.61
4057.03–4524.89)
100,000,
respectively.
highest
occurred
high-sociodemographic
index
(SDI)
regions
(232744.64,
95
206887.07–261694.81)
whereas
low-SDI
(9261.1,
8741.61–9820.86)
100,000.
ASDRs
0.28
0.09–0.61)
28.67
25.92–31.07)
observed
regions,
with
1.1
0.08–2.78)
70.68
62.56–78.62)
From
for
decreased,
AAPCs
−0.17
CI:
−0.16
%)
−1.28
−1.37
−1.22
%),
also
decreased
(−3.39
URIs;
−2.46
LRIs).
However,
during
COVID-19
pandemic,
increased
many
countries,
especially
high-SDI
(rate
difference
before
pandemic
2210.19
100,000.)
ASIR:
111.26
100,000).
related
ARIs
have
over
past
32
years.
it
remains
a
significant
public
health
concern,
particularly
due
notable
high
SDI
associated
low
regions.
Furthermore,
an
increase
high-
highlighting
need
attention.