Researchers identified mutations in the PfCRT protein, found in the malaria parasite’s digestive compartment, as the source of resistance to the frontline malaria drug piperaquine (or PPQ). Malaria affects over 200 million people every year around the globe.
PPQ works by entering and changing the parasite’s PfCRT proteins that line the digestive compartment. PPQ effectively allows the parasite to poison itself from the toxic waste formed from digested hemoglobin. Researchers used an imaging technique to show how resistant parasites use a variant of PfCRT protein to expel PPQ out of the digestive compartment.
To confirm the images, researchers made more mutations specific to the protein’s central cavity, which affected its ability to bind and transport PPQ, and expel the drug from the digestive compartment.
These findings, published in Nature, allow researchers to predict how resistance will arise around the world and develop new methods to restore the potency of antimalarial drugs. The study was partly funded by NHLBI.