Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response

• Main Authors: Zhu, Lei, van der Pluijm, Rob W., Kucharski, Michal, Nayak, Sourav, Tripathi, Jaishree, White, Nicholas J., Day, Nicholas P. J., Faiz, Abul, Phyo, Aung Pyae, Amaratunga, Chanaki, Lek, Dysoley, Ashley, Elizabeth A., Nosten, François, Smithuis, Frank, Ginsburg, Hagai, von Seidlein, Lorenz, Lin, Khin, Imwong, Mallika, Chotivanich, Kesinee, Mayxay, Mayfong, Dhorda, Mehul, Nguyen, Hoang Chau, Nguyen, Thuy Nhien Thanh, Miotto, Olivo, Newton, Paul N., Jittamala, Podjanee, Tripura, Rupam, Pukrittayakamee, Sasithon, Peto, Thomas J., Hien, Tran Tinh, Dondorp, Arjen M., Bozdech, Zbynek
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Biological sciences; Antimalarial Agent; Drug Resistance
• Online Access: https://hdl.handle.net/10356/160903
• Institution: Nanyang Technological University

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 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.