Malaria is a disease that kills 500 000 people yearly. The disease causing agent, Plasmodium falciparum, has evolved resistance to every antimalarial compound available in the field. High-throughput screens of hundreds of thousands of compounds to identify inhibitors of P. falciparum growth have been employed in an effort to identify novel antimalarial compounds. One particular protein, the Na+-efflux transporter PfATP4, appears to be the target of several potent antimalarial compounds identified in the high-throughput screens. Three of the compounds identified in the screens have entered the clinical pipeline.
I will present the findings of a phylogenetic analysis that suggests that PfATP4 belongs to a unique subgroup of type II P-type ATPases that is present only in apicomplexan parasites and their closest relatives. The absence of a human homologue for PfATP4 is good news for drug development. I will then discuss the effect of inhibiting PfATP4 on parasite physiology, with a focus on parasite Na+ content and volume. Finally, I will present the findings of a screen that I performed to identify novel PfATP4-associated compounds.