Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance

Title
Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance
Authors
Mok, S; Ashley, EA; Ferreira, PE; Zhu, L; Lin, ZT; Yeo, T; Chotivanich, K; Imwong, M; Pukrittayakamee, S; Dhorda, M; Nguon, C; Lim, P; Amaratunga, C; Suon, S; Hien, TT; Htut, Y; Faiz, MA; Onyamboko, MA; Mayxay, M; Newton, PN; Tripura, R; Woodrow, CJ; Miotto, O; Kwiatkowski, DP; Nosten, F; Day, NPJ; Preiser, PR; White, NJ; Dondorp, AM; Fairhurst, RM; Bozdech, Z
Keywords
PLASMODIUM-FALCIPARUM MALARIA; DIHYDROARTEMISININ-PIPERAQUINE; WESTERN CAMBODIA; CLEARANCE RATE; PROVINCE; PROTEIN; VIVAX
Issue Date
2015
Publisher
SCIENCE
Citation
SCIENCE;Science;23-Jan;2015;347;6220
Abstract
Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion.
URI
http://hdl.handle.net/11267/2313
ISSN
0036-8075
Appears in Collections:
3.University of Health Sciences > Faculty of postgraduate > Journal articles
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