Leishmaniasis is a spectrum of
diseases caused by
parasites of the genus
Leishmania that
affects millions of people around the world. During
infection, the
parasites use different
strategies to survive the host's defenses, including overcoming exposure to reactive
oxidant species (ROS), responsible for causing damage to
lipids,
proteins and
DNA. This damage especially
affects telomeres, which frequently results in
genome instability,
senescence and
cell death.
Telomeres are the physical ends of the
chromosomes composed of repetitive
DNA coupled with
proteins, whose function is to protect the
chromosomes termini and avoid end-fusion and nucleolytic degradation. In this
work, we induced acute
oxidative stress in promastigote forms of
Leishmania amazonensis by treating
parasites with 2 mM
hydrogen peroxide (H2O2) for 1 h, which was able to increase intracellular ROS levels. In addition,
oxidative stress induced
DNA damage, as confirmed by
8-oxodGuo quantification and
TUNEL assays and the
dissociation of LaRPA-1 from the 3' G-overhang, leading to
telomere shortening. Moreover, LaRPA-1 was observed to interact with newly formed C-rich single-stranded telomeric
DNA, probably as a consequence of the
DNA damage response. Nonetheless, acute
oxidative stress caused the
death of some of the L. amazonensis
population and induced
cell cycle arrest at the G2/
M phase in
survivor parasites, which were able to continue proliferating and replicating
DNA and became more resistant to
oxidative stress. Taken together, these results suggest that adaptation occurs through the selection of the fittest
parasites in terms of
repairing oxidative DNA damage at
telomeres and maintaining
genome stability in a stressful
environment.