Author:
Zhu Lei,van der Pluijm Rob W.,Kucharski Michal,Nayak Sourav,Tripathi Jaishree,Nosten François,Faiz Abul,Amaratunga Chanaki,Lek Dysoley,Ashley Elizabeth A,Smithuis Frank,Phyo Aung Pyae,Lin Khin,Imwong Mallika,Mayxay Mayfong,Dhorda Mehul,Chau Nguyen Hoang,Thuy Nhien Nguyen Thanh,Newton Paul N,Jittamala Podjanee,Tripura Rupam,Pukrittayakamee Sasithon,Peto Thomas J,Miotto Olivo,Seidlein Lorenz von,Hien Tran Tinh,Ginsburg Hagai,Day Nicholas PJ,White Nicholas J.,Dondorp Arjen M,Bozdech Zbynek
Abstract
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 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 summaryThe transcriptional profile that characterize artemisinin resistant infections with malaria parasites Plasmodium falciparum originates in the initial transcriptional response to the drug.
Publisher
Cold Spring Harbor Laboratory