New strategies to treat Leishmaniasis
Published: 13 July 2020
Research involving Professor Richard McCulloch and colleagues from iii has uncovered an unanticipated role for homologous recombination during replication of the plastic genome of the eukaryotic parasite Leishmania.
New research involving Professor Richard McCulloch and colleagues from iii has uncovered an unanticipated role for homologous recombination during replication of the plastic genome of the eukaryotic parasite Leishmania.
The study, a collaboration led by Dr Jeziel D. Damasceno and involving universities from Brazil, was recently published in PLoS Genetics.
Drug resistance acquisition is one of the major challenges in eradicating Leishmaniasis, the collection of diseases caused by Leishmania.
The plasticity of Leishmania’s genome allows the parasites to quickly alter its genome content and adapt to environmental changes, including in response to anti-leishmanial therapies.
The molecular peculiarities of the genome replication process underlying such genome plasticity in Leishmania is still little understood.
Dr Damasceno’s work revealed that loss of the key genome repair factor RAD51 dramatically changes the genome replication programme in Leishmania.
Because previous work has shown that RAD51 is an enzyme also required for Leishmania genome plasticity, this new research provides clues that suggest genome variability and genome replication are intimately connected processes in the parasite.
Dr Damasceno said: "We are excited by these findings because identification of such a central role for RAD51 in Leishmania’s genome replication provides an opening for us to uncover the wider cellular reactions that direct two critical survival mechanisms: genome plasticity and genome replication.
"In addition, because RAD51 is a recombinase enzyme for which inhibitors have been developed, such as for treating cancer, we have the opportunity to test if genome replication can be blocked, which may lead to new strategies to treat Leishmaniasis."
Prof McCulloch added: "It has been a pleasure to work with Jeziel on this project, which represents one thread of his EC Marie Sklodowska-Curie fellowship and provides yet more insight into how flexible and unorthodox genome replication is in the important human parasite Leishmania."
Conditional knockout of RAD51-related genes in Leishmania major reveals a critical role for homologous recombination during genome replication
- Jeziel D. Damasceno, João Reis-Cunha, Kathryn Crouch, Dario Beraldi, Craig Lapsley, Luiz R. O. Tosi, Daniella Bartholomeu, Richard McCulloch. Published: July 1, 2020 https://doi.org/10.1371/journal.pgen.1008828
This work was supported by the BBSRC and by the European Commission's Marie Sklodowska-Curie Individual Fellowship.
First published: 13 July 2020