Putrescine Depletion in Leishmania donovani Parasites Causes Immediate Proliferation Arrest Followed by an Apoptosis-like Cell Death
John W. Johnston,
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Jonathan Taylor,
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Surbhi Nahata
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et al.
Pathogens,
Journal Year:
2025,
Volume and Issue:
14(2), P. 137 - 137
Published: Feb. 2, 2025
The
polyamine
pathway
in
Leishmania
parasites
has
emerged
as
a
promising
target
for
therapeutic
intervention,
yet
the
functions
of
polyamines
remain
largely
unexplored.
Ornithine
decarboxylase
(ODC)
and
spermidine
synthase
(SPDSYN)
catalyze
sequential
conversion
ornithine
to
putrescine
spermidine.
We
previously
found
that
donovani
Δodc
Δspdsyn
mutants
exhibit
markedly
reduced
growth
vitro
diminished
infectivity
mice,
with
effect
being
most
pronounced
putrescine-depleted
mutants.
Here,
we
report
that,
polyamine-free
media,
∆odc
arrested
proliferation
replication,
while
∆spdsyn
showed
slow
replication
phenotype.
Starved
also
exhibited
marked
reduction
metabolism,
which
was
not
observed
starved
cells.
In
contrast,
both
displayed
mitochondrial
membrane
hyperpolarization.
Hallmarks
apoptosis,
specifically
DNA
fragmentation
modifications,
were
incubated
media.
These
results
show
depletion
had
an
immediate
detrimental
on
cell
growth,
metabolism
caused
apoptosis-like
death
Our
findings
establish
ODC
within
biosynthetic
treating
leishmaniasis.
Language: Английский
Defence Warriors: Exploring the crosstalk between polyamines and oxidative stress during microbial pathogenesis
Redox Biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 103648 - 103648
Published: April 1, 2025
Microbial
infections
have
been
a
widely
studied
area
of
disease
research
since
historical
times,
yet
they
are
cause
severe
illness
and
deaths
worldwide.
Furthermore,
by
pathogens
not
just
restricted
to
humans;
instead,
diverse
range
hosts,
including
plants,
livestock,
marine
organisms
fish,
significant
economic
losses
pose
threats
humans
through
their
transmission
in
the
food
chain.
It
is
now
believed
that
both
pathogen
host
contribute
outcomes
pathology.
Researchers
unravelled
numerous
aspects
host-pathogen
interactions,
offering
valuable
insights
into
physiological,
cellular
molecular
processes
factors
development
infectious
diseases.
Polyamines
key
regulating
human
ageing
health.
However,
often
overlooked
context
interactions
despite
playing
dynamic
role
as
defence
molecule
from
perspective
well
pathogen.
They
form
complex
network
interacting
with
several
molecules
within
cell,
reactive
oxygen
species
being
component.
This
review
presents
thorough
overview
current
knowledge
polyamines
intricate
infection
multiple
hosts.
Interestingly,
covers
interplay
commensals
involving
species,
highlighting
an
unexplored
this
field.
From
future
perspective,
oxidative
stress
microbial
pathogenesis
fascinating
widens
scope
developing
therapeutic
strategies
combat
deadly
infections.
Language: Английский