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

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 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.

• Authors: Lei Zhu, Rob W van der Pluijm, Michal Kucharski, Sourav Nayak, Jaishree Tripathi, Nicholas J White, Nicholas P J Day, Abul Faiz, Aung Pyae Phyo, Chanaki Amaratunga, Dysoley Lek, Elizabeth A Ashley, François Nosten, Frank Smithuis, Hagai Ginsburg, Lorenz von Seidlein, Khin Lin, Mallika Imwong, Kesinee Chotivanich, Mayfong Mayxay, Mehul Dhorda, Hoang Chau Nguyen, Thuy Nhien Thanh Nguyen, Olivo Miotto, Paul N Newton, Podjanee Jittamala, Rupam Tripura, Sasithon Pukrittayakamee, Thomas J Peto, Tran Tinh Hien, Arjen M Dondorp, Zbynek Bozdech
• Journal: Communications biology (Commun Biol) Vol. 5 Issue 1 Pg. 274 (03 28 2022) ISSN: 2399-3642 [Electronic] England
• PMID: 35347215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Antimalarials
• Artemisinins
• artemisinin

Topics

• Animals
• Antimalarials (pharmacology, therapeutic use)
• Artemisinins
• Drug Resistance (genetics)
• Malaria, Falciparum (drug therapy, parasitology)
• Parasites
• Plasmodium falciparum