Mechanism of artemisinin resistance

The emergence of artemisinin resistance is a major threat to world-wide malaria treatment and control and although artemisinins have been linked with a variety of cellular factors, there has been no consensus on the relevant biochemical targets or mechanisms underpinning resistance. Here Kasturi Haldar and colleagues show that artemisinins target the parasite phosphatidylinositol-3-kinase (PfPI3K) to inhibit the production of phosphatidylinositol 3-phosphate (PI3P). Mutation in PfKelch13, a previously identified resistance marker, increases levels of PfPI3K in both clinically derived strains and in engineered laboratory parasites. This work points to PfPI3K as the key mediator of artemisinin resistance and a target for malaria elimination.