Plasmodium falciparum lipid metabolism and the search for drug targets

Orateur : Henri VIAL (Dynamique des Interactions Normales et Pathologiques, CNRS UMR 5235, Université Montpellier 2, Montpellier)

Lipids are of crucial importance for pathogens. They serve as a cellular building block, signaling molecules and pathogenesis effectors. Phospholipids are the major lipid component of malaria parasites. Our studies are geared towards the functional characterization of molecular cellular and membrane events that lead to membrane biogenesis in Plasmodium development within host cells. Tremendous advances have been made in the understanding of the synthesis pathways for phospholipid acquisition through a bewildering variety of even novel metabolic pathways, in clarifying the processes that could be major and/or essential for the differentiation and development of these parasites, and finally in determining the original features in terms of biological processes versus mammalian cells. Trancriptomics and metabolomics studies show that the parasite changes dramatically as it transits through the various stages of its life cycle. The program provides opportunities for drug development and has resulted in the development of a new chemotherapy strategy against P. falciparum malaria, targeting phospholipid plasmodial metabolism. The most advanced antimalarial drug development program targeting the parasite metabolism is focused on inhibition of de novo phosphatidylcholine biosynthesis. The choline analog albitiazolium, which is currently being clinically tested against severe malaria, represents a new type of antimalarial whose mechanism of action differs from those currently being marketed.

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