Deeper into hemozoin formation pathway of Plasmodium falciparum

Abstract

Plasmodium falciparum malaria remains a public health problem, accounting for half millions of lives yearly. Artemisinin-combination therapies are the front-line treatment against malaria, which efficacy is now threatened by parasite’s-acquired resistance. Most antimalarial drugs target the symptomatic intra-erythrocytic stage of infection. During parasite development inside the human erythrocytes, parasites digest hemoglobin as a source of nutrients. This causes the release of toxic free heme, which the parasite detoxifies into inert crystals, called hemozoin. It is known that parasites with abnormalities in this pathway are committed to death. However, despite its importance, the orchestration of hemoglobin digestion into hemozoin formation has not been entirely resolved, and its players have not been identified. Through reverse genetics, we explored the role of P. falciparum aspartic proteases and other genes thought to be involved in the formation of hemozoin and their capacity to modulate drug response. We believe that a deeper understanding of this pathway is of great interest and relevant for the identification of new targets, both for diagnosis and for the development of antimalarial drugs. Furthermore, it will also provide insights into drug resistance, overall contributing for better malaria control and management.