[Targeting malaria parasite at the level of apicoplast: an update]

Abstract

In 1996, the discovery of a relic chloroplast in Plasmodium and Toxoplasma cells has strongly changed our vision of these parasites in the "Tree of Life", and has opened an unexpected new field of investigation in the search for antiparasitic treatments, including antimalarials. This review details our current understanding of the sophisticated evolution of the parasites of the Apicomplexa phylum and briefly covers a decade of research and development in drug discovery, trying to target the malaria parasite at the level of its plant-like organelle. Fifteen years after the discovery of the apicoplast and ten years after the publication of the genome of Plasmodium falciparum, it seems that we have completed a first phase of tests of available antibiotics and herbicides. In the human host, the liver phase is the only parasitic stage, for which biological functions harbored by the apicoplast, such as fatty acid biosynthesis, seem indispensable. During the erythrocytic phase, recent results have focused the attention on the processes controlling the biogenesis of the apicoplast, and one of the functions harbored by the apicoplast, i.e. the biosynthesis of isoprenoids, as major -promising targets for future treatments.