Scientists strike back: are we outsmarting malaria?

Climate change allows tropical infectious diseases such as malaria to spread to new areas in the world. An additional problem is the emerging resistance of the malaria pathogen to current medication. Scientists discovered how this resistance is established. They published their findings in the scientific journal Science.

Anti-malaria drug Artemisinin
Malaria is caused by the single-celled parasite Plasmodium falciparum, which multiplies in red blood cells of its host. The first defense against malaria are drugs that contain the active substance Artemisinin. This drug kills the Plasmodium parasite by attacking its protein disposal system as well as other proteins. But this medication is threatened now that Plasmodium increasingly seems insensitive to Artemisinin. Previous research showed that small changes in a protein of the pathogen are associated with Artemisinin resistance. The exact function of this protein, called Kelch13, was still unknown.

Pathogen seals own fate
Plasmodium feeds on the haemoglobin in the blood of its host. Researchers from Hamburg and Nijmegen discovered that the parasite’s Kelch13 protein plays a role in this. The protein removes hemoglobin from the red blood cell and transports it to the “stomach” of the Plasmodium through a process called endocytosis. After digestion, degradation products remain. Precisely these products are needed to activate the malaria drug Artemisinin.

“The pathogen must pay a hefty price for resistance”

Small mutations
Plasmodium parasites make smart use of the fact that they are in control of Artemisinin activation. Over time, small changes occurred in the Kelch-13 protein, making the protein less active. Less active Kelch-13 proteins produce fewer breakdown products so the malaria drug is not activated. However, the pathogen must pay a hefty price for the resistance. As it eats less haemoglobin, it receives less nutrients. This slows down its growth at a certain stage and induces more stress.

Combating malaria
Determining the resistance mechanism of Plasmodium is an important step in combating malaria. “We suspect that this will help find ways to neutralize the resistance,” the authors say.

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