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

Author:

Mok Sachel1,Ashley Elizabeth A.23,Ferreira Pedro E.1,Zhu Lei1,Lin Zhaoting1,Yeo Tomas1,Chotivanich Kesinee4,Imwong Mallika5,Pukrittayakamee Sasithon4,Dhorda Mehul367,Nguon Chea8,Lim Pharath89,Amaratunga Chanaki9,Suon Seila8,Hien Tran Tinh10,Htut Ye11,Faiz M. Abul12,Onyamboko Marie A.13,Mayxay Mayfong1415,Newton Paul N.2314,Tripura Rupam2,Woodrow Charles J.23,Miotto Olivo21617,Kwiatkowski Dominic P.1617,Nosten François318,Day Nicholas P. J.23,Preiser Peter R.1,White Nicholas J.23,Dondorp Arjen M.23,Fairhurst Rick M.9,Bozdech Zbynek1

Affiliation:

1. School of Biological Sciences, Nanyang Technological University, Singapore.

2. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

3. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

4. Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

5. Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

6. WorldWide Antimalarial Resistance Network (WWARN), Asia Regional Centre, Mahidol University, Bangkok, Thailand.

7. WorldWide Antimalarial Resistance Network, University of Maryland School of Medicine, Baltimore, MD, USA.

8. National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.

9. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

10. Oxford University Clinical Research Unit (OUCRU), Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.

11. Department of Medical Research, Lower Myanmar, Yangon, Myanmar.

12. Malaria Research Group & Dev Care Foundation, Dhaka, Bangladesh.

13. Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.

14. Lao–Oxford–Mahosot Hospital–Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Lao PDR.

15. Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Lao PDR.

16. Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK.

17. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

18. Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

Abstract

Mechanisms propelling drug resistance If it were to spread, resistance to the drug artemisinin would seriously derail the recent gains of global malaria control programs (see the Perspective by Sibley). Mutations in a region called the K13-propeller are predictive for artemisinin resistance in Southeast Asia. Mok et al. looked at the patterns of gene expression in parasites isolated from more than 1000 patients sampled in Africa, Bangladesh, and the Mekong region. A range of mutations that alter protein repair pathways and the timing of the parasite's developmental cycle were only found in parasites from the Mekong region. Straimer et al. genetically engineered the K13 region of parasites obtained from recent clinical isolates. Mutations in this region were indeed responsible for the resistance phenotypes. Science , this issue p. 431 , p. 428 ; see also p. 373

Funder

National Institute of Allergy and Infectious Diseases (NIAID)

Bill & Melinda Gates Foundation

Singapore National Medical Council

Wellcome Trust Sanger Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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