Abstract The emergence and spread of artemisinin resistant Plasmodium falciparum , first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria eliminations ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016-2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodeling and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex. One sentence summary The transcriptional profile that characterize artemisinin resistant infections with malaria parasites Plasmodium falciparum originates in the initial transcriptional response to the drug.

The mechanism of artemisinin resistance of Plasmodium falciparum malaria parasites originates in their initial transcriptional response