bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 10, 2024
Abstract
Antimicrobial
resistant
pathogens
such
as
Escherichia
coli
sequence
type
131
(ST131)
pose
a
serious
threat
to
public
health
globally.
In
the
United
States,
ST131
acquired
multiple
antimicrobial
resistance
(AMR)
genes
and
rapidly
grew
its
current
high
prevalence
in
healthcare
settings.
Notably,
this
coincided
with
introduction
widespread
use
of
antibiotics
fluoroquinolones,
suggesting
AMR
major
driver
ST131’s
expansion.
Yet,
within
ST131,
there
remains
considerable
diversity
between
strains
profiles
their
repertoires
virulence
factors,
stress
plasmids,
other
accessory
elements.
Understanding
which
genomic
features
contribute
competitive
advantage
relative
effects
on
population-level
fitness
therefore
poses
challenge.
Here
we
phylodynamic
birth-death
models
estimate
different
lineages
from
bacterial
phylogenies.
By
extending
these
methods
allow
shape
fitness,
further
quantify
contribution
individual
fitness.
Our
analysis
indicates
that
while
many
elements,
including
various
genes,
have
all
contributed
substantially
rapid
growth,
increases
are
largely
attributable
mutations
gyrase
A
confer
fluoroquinolones.
Author
summary
is
pandemic
lineage
E.
has
spread
globally
now
responsible
for
large
percentage
blood
urinary
tract
infections
cannot
be
treated
common
antibiotics.
While
antibiotic
undoubtedly
given
edge,
importance
compared
factors
shaping
pathogen’s
growth
or
transmission
potential
(i.e.
fitness)
often
difficult
measure
natural
Here,
present
method
allows
us
look
at
entire
spectrum
determining
each
component
overall
results
suggest
widely
used
class
antibiotics,
provides
disproportionately
more
moderate
effects.
what
determines
insights
can
curb
monitor
emerging
due
shared
enhancing
attributes.
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(51)
Опубликована: Дек. 14, 2023
Conjugative
plasmids
play
a
key
role
in
the
dissemination
of
antimicrobial
resistance
(AMR)
genes
across
bacterial
pathogens.
AMR
are
widespread
clinical
settings,
but
their
distribution
is
not
random,
and
certain
associations
between
clones
particularly
successful.
For
example,
globally
spread
carbapenem
plasmid
pOXA-48
can
use
wide
range
enterobacterial
species
as
hosts,
it
usually
associated
with
small
number
specific
Molecular Systems Biology,
Год журнала:
2022,
Номер
19(2)
Опубликована: Дек. 27, 2022
Abstract
Plasmid
fitness
is
directed
by
two
orthogonal
processes—vertical
transfer
through
cell
division
and
horizontal
conjugation.
When
considered
individually,
improvements
in
either
mode
of
can
promote
how
well
a
plasmid
spreads
persists.
Together,
however,
the
metabolic
cost
conjugation
could
create
tradeoff
that
constrains
evolution.
Here,
we
present
evidence
for
presence,
consequences,
molecular
basis
conjugation‐growth
across
40
plasmids
derived
from
clinical
Escherichia
coli
pathogens.
We
discover
most
operate
below
efficiency
threshold
major
growth
effects,
indicating
strong
natural
selection
vertical
transfer.
Below
this
threshold,
E.
demonstrates
remarkable
tolerance
to
over
four
orders
magnitude
change
efficiency.
This
fades
as
nutrients
become
scarce
attracts
greater
share
host
resources.
Our
results
provide
insight
into
evolutionary
constraints
directing
strategies
combat
spread
antibiotic
resistance.
Plasmids,
extrachromosomal
DNA
molecules
commonly
found
in
bacterial
and
archaeal
cells,
play
an
important
role
genetics
evolution.
Our
understanding
of
plasmid
biology
has
been
furthered
greatly
by
the
development
mathematical
models,
there
are
many
questions
about
plasmids
that
models
would
be
useful
answering.
In
this
review,
we
present
introductory,
yet
comprehensive,
overview
suitable
for
modellers
unfamiliar
with
who
want
to
get
up
speed
begin
working
on
plasmid-related
models.
addition
reviewing
diversity
genes
they
carry,
their
key
physiological
functions,
interactions
between
host,
also
highlight
selected
topics
may
particular
interest
areas
where
is
a
need
theoretical
development.
The
world
holds
great
variety
subjects
will
biologists,
introducing
new
subject
help
expand
existing
body
theory.
PLoS Genetics,
Год журнала:
2025,
Номер
21(2), С. e1011560 - e1011560
Опубликована: Фев. 7, 2025
Plasmid
conjugation
is
a
major
route
for
the
dissemination
of
antibiotic
resistances
and
adaptive
genes
among
bacterial
populations.
Obtaining
precise
rates
thus
key
to
understanding
how
spread.
typically
modeled
as
density-dependent
process,
where
formation
new
transconjugants
depends
on
rate
encounters
between
donor
receptor
cells.
By
analyzing
dynamics
at
different
cell
concentrations,
here
we
show
that
this
assumption
only
holds
very
low
densities.
At
higher
becomes
limited
by
engagement
time,
interval
required
two
successful
matings.
therefore
follows
Holling´s
Type
II
functional
response,
characterized
encounter
which
represent,
respectively,
density
frequency-dependent
limits
plasmid
transmission.
Our
results
demonstrate
these
parameters
are
characteristic
transfer
machinery,
rather
than
entire
genome,
they
robust
environmental
transcriptional
perturbation.
Precise
parameterization
will
contribute
better
propagation
antimicrobial
resistances.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 1, 2023
Abstract
The
ability
to
effectively
represent
microbiome
dynamics
is
a
crucial
challenge
in
their
quantitative
analysis
and
engineering.
By
using
autoencoder
neural
networks,
we
show
that
microbial
growth
can
be
compressed
into
low-dimensional
representations
reconstructed
with
high
fidelity.
These
embeddings
are
just
as
effective,
if
not
better,
than
raw
data
for
tasks
such
identifying
bacterial
strains,
predicting
traits
like
antibiotic
resistance,
community
dynamics.
Additionally,
demonstrate
essential
dynamical
information
of
these
systems
captured
far
fewer
variables
traditional
mechanistic
models.
Our
work
suggests
machine
learning
enable
the
creation
concise
high-dimensional
facilitate
gain
new
biological
insights.
ACS Synthetic Biology,
Год журнала:
2024,
Номер
13(4), С. 1142 - 1151
Опубликована: Апрель 3, 2024
The
metabolic
engineering
of
microbes
has
broad
applications,
including
biomanufacturing,
bioprocessing,
and
environmental
remediation.
introduction
a
complex,
multistep
pathway
often
imposes
substantial
burden
on
the
host
cell,
restraining
accumulation
productive
biomass
limiting
efficiency.
One
strategy
to
alleviate
is
division
labor
(DOL)
in
which
different
subpopulations
carry
out
parts
work
together
convert
substrate
into
final
product.
However,
maintenance
engineered
challenging
due
competition
convoluted
interstrain
population
dynamics.
Through
modeling,
we
show
that
dynamic
(DDOL),
define
as
DOL
between
indiscrete
populations
capable
reversible
interchange,
can
overcome
these
limitations
enable
robust
burdensome,
pathways.
We
propose
DDOL
be
mediated
by
horizontal
gene
transfer
(HGT)
use
plasmid
genomics
uncover
evidence
utilized
natural
microbial
communities.
Our
suggests
bioengineers
harness
HGT
stabilize
synthetic
pathways
communities,
enabling
development
systems
for
deployment
variety
contexts.
Antimicrobial Agents and Chemotherapy,
Год журнала:
2024,
Номер
68(10)
Опубликована: Авг. 28, 2024
It
has
been
shown
that
an
evolutionary
tradeoff
between
vertical
(host
growth
rate)
and
horizontal
(plasmid
conjugation)
transmissions
contributes
to
global
plasmid
fitness.
As
conjugative
IncC
plasmids
are
important
for
the
spread
of
multidrug
resistance
(MDR),
in
a
broad
range
bacterial
hosts,
we
investigated
two
multidrug-resistant
according
their
backbones
MDR-region
rearrangements,
upon
entry
into
new
host.
We
observed
genome
deletions
after
conjugation
three
diverse
natural
Abstract
Bacterial
conjugation,
wherein
DNA
is
transferred
between
cells
through
direct
contact,
highly
prevalent
in
complex
microbial
communities
and
responsible
for
spreading
myriad
genes
related
to
human
environmental
health.
Despite
their
importance,
much
remains
unknown
regarding
the
mechanisms
driving
spread
persistence
of
these
plasmids
situ.
Studies
have
demonstrated
that
transferring,
acquiring,
maintaining
a
plasmid
imposes
significant
metabolic
burden
on
host.
Simultaneously,
emerging
evidence
suggests
presence
conjugative
can
also
provide
both
obvious
unexpected
benefits
host
local
community.
Combined,
this
highlights
continuous
cost‐benefit
tradeoff
at
population
level,
likely
contributing
overall
abundance
long‐term
persistence.
Yet,
while
burdens
causes,
are
widely
studied,
attendant
potential
advantages
less
clear.
Here,
we
summarize
current
perspectives
plasmids’
then
highlight
lesser‐appreciated
yet
critical
plasmid‐mediated
may
provide.
We
argue
largely
unexplored
fundamental
theory
populations
engineering
applications
therefore
warrants
further
detailed
study.