What exactly does the PfK13 mutation in Plasmodium falciparum change?

Abstract

The emergence and development of artemisinin resistance threaten global malaria control and elimination goals, thereby prompting research on the mechanisms of malaria parasite resistance. The mutation of Plasmodium falciparum Kelch 13 ( PfK13) protein is associated with artemisinin resistance, but the unique or common mechanism by which it leads to this resistance is unclear. By analyzing the different effects of PfK13 mutation on the P. falciparum transcriptome and proteome at the different stages, we found that PfK13 mutation did not significantly change glycolysis, TCA, pentose phosphate pathway (PPP) and oxidative phosphorylation but reduced the expression of reproduction- and DNA synthesis-related genes. Moreover, the reduced number of the merozoite, decreased amount of hemozoin, and slowed growth of P. falciparum 3D7C580Y were consistent with the changes, suggesting that the PfK13 mutation reduces hemoglobin ingestion, leading to artemisinin resistance, likely by decreasing the parasites' need for haem and iron. This study helps elucidate the mechanism of artemisinin resistance caused by the PfK13 mutation.