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

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 MayxayMehul 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

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

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.
Original languageEnglish
Article number274
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022

Cite this