Mechanisms of Plasmodium resistance and therapeutic targets

Malaria is a major public health problem worldwide, with almost 600,000 deaths per year, most of them children under the age of 5. The treatment of this disease, caused mostly by the Plasmodium falciparum parasite, has been the main focus of our team’s work for many years. The successive resistance of this parasite to antimalarial drugs means that the therapeutic arsenal must be constantly renewed. In this context, we are looking at resistance to the artemisinin family (the main antimalarial drugs used), which is currently emerging in Africa, where 90% of malaria deaths are concentrated.

Our work has already led to the selection of the first artemisinin-resistant laboratory strain (F32-ART), to the demonstration that resistant parasites enter quiescence (or dormancy) during treatment, and to the identification of the pfk13 gene polymorphism as a molecular marker for this resistance.

We have recently demonstrated the involvement of redox, epigenetic and biochemical mechanisms in parasite resistance to artemisinins. We are continuing to explore the changes that occur in resistant parasites in order to identify relevant therapeutic targets for the design of drug candidates capable of eliminating artemisinin-resistant parasites.