Indispensable malaria genes

A critical assessment of new opportunities for drug discovery to treat malaria Malaria parasites, carried by mosquitoes and transmitted to humans, infect ∼200 million individuals and cause ∼500,000 deaths each year ( 1 ). Fifteen years after identifying the genome sequence of a malaria-causing parasite, Plasmodium falciparum , malaria treatments still rely heavily on chemicals derived from natural products that were used centuries ago ( 2 ). With cell-based functional assays, the gap between genome sequences of Plasmodium spp. and the identification of valuable new therapeutics may be reduced by determining which genes are essential for parasite propagation in the disease-causing blood stage of the parasite life-cycle. The most potent and clinically useful antimalarial drugs rapidly eliminate parasites growing in red blood cells (RBCs). On page 506 of this issue, Zhang et al. ( 3 ) report a mutagenesis screen on P. falciparum cultured in human RBCs, identifying 2680 indispensable parasite genes, which may contain antimalarial drug targets. However, it is important to critically assess what fraction of these essential genes will be good drug targets and how one should prioritize such targets for drug discovery.