Pipettes And Politics

Malaria exerts a devastating impact on communities in the Global South, with upwards of 600,000 deaths yearly, primarily young African children. Using genetic approaches, we have explored the molecular basis of Plasmodium falciparum antimalarial drug resistance, which poses a constant threat to malaria treatment and control efforts. Using a genetic cross, we earlier identified that mutations in PfCRT conferred parasite resistance to chloroquine, the former first-line antimalarial drug. Structural and functional studies reveal that these mutations enable this transporter of globin-derived peptides to efflux chloroquine away from its heme target in parasitized erythrocytes. We also identified novel PfCRT variants that mediate resistance to piperaquine, a first-line combination partner drug that recently failed across Southeast Asia. We and others have also shown that mutations in Kelch13 are causal for parasite resistance to artemisinin, the core component of all current combination therapies, and have identifi