Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response
Zhu L., van der Pluijm RW., Kucharski M., Nayak S., Tripathi J., White NJ., Day NPJ., Faiz A., Phyo AP., Amaratunga C., Lek D., Ashley EA., Nosten F., Smithuis F., Ginsburg H., von Seidlein L., Lin K., Imwong M., Chotivanich K., Mayxay M., Dhorda M., Nguyen HC., Nguyen TNT., Miotto O., Newton PN., Jittamala P., Tripura R., Pukrittayakamee S., Peto TJ., Hien TT., Dondorp AM., Bozdech Z.
AbstractThe 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 elimination 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 remodelling, 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.