World Malaria Day – A Single Protein Opens the Way for Drug Screening

A recent Nature paper revealed how the discovery of a novel protein, AP-2G, has opened the way for improvements in specific drug development to fight the deadly disease malaria. The AP-2G protein acts as a master switch that triggers the development of sexual forms of the malaria parasite, a stage essential for the spread of the disease.

Completion of sexual development is essential for Plasmodium malariae parasites to be transmitted through mosquitoes. Sexual reproduction is a vulnerable stage of the parasite's complicated lifecycle. This stage can only occur in the gut of the mosquito after it has sucked the precursor parasite cells out of a person's blood. Until publication of this new research, the molecular mechanism of the commitment and completion of the parasite’s sexual development was unknown. The novel protein, PbAP2-G, a member of the apicomplexan AP2 (ApiAP2) family of DNA-binding proteins, is essential for the commitment of asexually replicating forms to sexual development.

Preventing transmission
Data from this research suggests a positive feedback loop mechanism in gametocytogenesis in Plasmodium. This mechanism is consistent with involvement of PbAP2-G and demonstrates that the mechanism could be exploited to prevent the transmission of this destructive parasite.

Researchers involved in this study, from the Welcome Trust Sanger Institute, the University of Glasgow and Penn State University, believe that the discovery of PbAP2-G opens the way to the development of screens for effective drugs that could disable commitment to sexual development and prevent transmission.