Resistance of malaria parasites against artemisinin explained

7 January 2020

Malaria parasites that are resistant to the commonly used malaria medicine artemisinin are a growing problem. How these parasites become resistant has now been uncovered by the collaborative effort of researchers in the group of Richard Bartfai, theme Infectious diseases and global health, and from the Bernhard Nocht Institute for Tropical Medicine (BNITM) in Hamburg. These important findings have been published in Science. 

Plasmodium falciparum, the parasite that causes malaria, infects more than 200 million people, resulting in more than 400,000 deaths each year. Artemisinin is usually used in combination with other medicines to treat the disease. However, the growing resistance of the malaria parasite to the medicine is putting its effectiveness at risk. It was already known that mutations in the protein Kelch13 in the parasite coincide with artemisinin resistance, but it was still unclear exactly what role this mutated protein plays in this process. Together with colleagues from BNITM in Hamburg, Richard Bartfai’s team succeeded in revealing the molecular mechanism behind artemisinin resistance in malaria parasites. Malaria parasites cause the disease while living in red blood cells, where they feed on hemoglobin. The researchers have found that parasites with a mutation in the gene encoding the protein Kelch13 are less able to take up hemoglobin. As a result, the parasite produces fewer hemoglobin degradation products - and these degradation products are critical to activate artemisinin. Because the medicine is not sufficiently activated in parasites with the Kelch13-mutation, the medicine is no longer able to kill the parasite, causing resistance.

This discovery is a breakthrough in our understanding of artemisinin resistance, which might help developing novel strategies to counteract resistance in parasites with the help of other medicines.