Drug target to fight malaria transmission identified

The fight against malaria has slowed as a result of mosquitoes developing resistance to insecticides, calling for new interventions. Now, researchers in the U.K. have found what might be an ideal drug target to fight malaria transmission: the AQP2 gene of the malaria parasite Plasmodium.

Researchers identified the gene after a comprehensive screening of thousands of Plasmodium genes. First, they removed hundreds of genes one by one, making mutants by altering the parasite’s DNA and giving each mutant a specific tag. Then, they tested these mutants using mosquitoes to figure out which genes are really important for the parasite’s survival in the mosquitoes. Explaining the findings in the Proceedings of the National Academy of Sciences (bit.ly/malaria-target), Alexander James Bailey, one of two first authors and a PhD candidate at Imperial College London, U.K., says that AQP2 is “crucial for the growth and transmission of malaria parasites in mosquitoes, and its uniqueness makes it a promising target for drug development to combat malaria transmission.”

The AQP2 gene codes for aquaporin 2 protein, which is responsible for moving water (and potentially other substances) within the parasite and plays a crucial role in helping it grow inside mosquitoes to produce the parasitic forms (‘sporozoites’) injected into humans in mosquito bites. “Drugs that block the transportation channel probably should stop the parasite from being able to transmit through the mosquito,” explained Bailey. While the researchers are still trying to understand AQP2’s exact function, its role in the growth and reproduction stages of the malaria parasite within mosquitoes suggests that blocking it could hinder transmission. Also, since the AQP2 in malaria parasites differs significantly from human proteins, it becomes a promising and specific target for developing drugs that could potentially block the transmission of malaria.

Bailey adds that the lab actively engages in genetically modifying mosquitoes to combat malaria. Identifying drugs to block AQP2 and understanding its function represent crucial next steps in the research.

Shailja Singh, Professor at the Jawaharlal Nehru University in New Delhi, who was not involved in the study, says, “The development of drugs targeting AQP2 will demonstrate negligible toxicity towards the host cells.” An earlier study (bit.ly/malaria-erythritol), Singh says, had “repurposed a tabletop sweetener called erythritol as aquaporin permeant, and demonstrated potent antimalarial and transmission blocking activity.” She added, “The activity of erythritol against AQP2 is worth exploration in future.”

As the world grapples with malaria, AQP2 appears to be a potential game-changer for effective strategies against the global health threat.