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

Sachel Mok | Zendy; Elizabeth A. Ashley | Zendy; Pedro Eduardo Ferreira | Zendy; Lei Zhu | Zendy; Zhaoting Lin | Zendy; Tomas Yeo | Zendy; Kesinee Chotivanich | Zendy; Mallika Imwong | Zendy; Sasithon Pukrittayakamee | Zendy; Mehul Dhorda | Zendy; Chea Nguon | Zendy; Pharath Lim | Zendy; Chanaki Amaratunga | Zendy; Seila Suon | Zendy; Tran Tinh Hien | Zendy; Ye Htut | Zendy; Mohammad Abul Faiz | Zendy; Marie Onyamboko | Zendy; Mayfong Mayxay | Zendy; Paul N. Newton | Zendy; Rupam Tripura | Zendy; Charles J. Woodrow | Zendy; Olivo Miotto | Zendy; Dominic Kwiatkowski | Zendy; François Nosten | Zendy; Nicholas Day | Zendy; Peter R. Preiser | Zendy; Nicholas J. White | Zendy; Arjen M. Dondorp | Zendy; Rick M. Fairhurst | Zendy; Zbynek Bozdech | Zendy

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

Author(s) -

Sachel Mok,

Elizabeth A. Ashley,

Pedro Eduardo Ferreira,

Lei Zhu,

Zhaoting Lin,

Tomas Yeo,

Kesinee Chotivanich,

Mallika Imwong,

Sasithon Pukrittayakamee,

Mehul Dhorda,

Chea Nguon,

Pharath Lim,

Chanaki Amaratunga,

Seila Suon,

Tran Tinh Hien,

Ye Htut,

Mohammad Abul Faiz,

Marie Onyamboko,

Mayfong Mayxay,

Paul N. Newton,

Rupam Tripura,

Charles J. Woodrow,

Olivo Miotto,

Dominic Kwiatkowski,

François Nosten,

Nicholas Day,

Peter R. Preiser,

Nicholas J. White,

Arjen M. Dondorp,

Rick M. Fairhurst,

Zbynek Bozdech

Publication year - 2014

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1260403

Subject(s) - artemisinin , malaria , mechanism (biology) , transcriptome , biology , drug resistance , population , resistance (ecology) , plasmodium falciparum , environmental health , microbiology and biotechnology , ecology , genetics , gene , medicine , immunology , gene expression , philosophy , epistemology

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.

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