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The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background

Author

Listed:
  • Lei Zhu

    (Nanyang Technological University)

  • Jaishree Tripathi

    (Nanyang Technological University)

  • Frances Maureen Rocamora

    (Nanyang Technological University)

  • Olivo Miotto

    (Mahidol University
    University of Oxford
    University of Oxford
    Wellcome Trust Sanger Institute)

  • Rob Pluijm

    (Mahidol University
    University of Oxford)

  • Till S. Voss

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Sachel Mok

    (Columbia University)

  • Dominic P. Kwiatkowski

    (Mahidol University
    University of Oxford
    University of Oxford
    Wellcome Trust Sanger Institute)

  • François Nosten

    (Mahidol University
    Mahidol University)

  • Nicholas P. J. Day

    (Mahidol University
    University of Oxford)

  • Nicholas J. White

    (Mahidol University
    University of Oxford)

  • Arjen M. Dondorp

    (Mahidol University
    University of Oxford)

  • Zbynek Bozdech

    (Nanyang Technological University)

Abstract

The predisposition of parasites acquiring artemisinin resistance still remains unclear beyond the mutations in Pfk13 gene and modulation of the unfolded protein response pathway. To explore the chain of casualty underlying artemisinin resistance, we reanalyze 773 P. falciparum isolates from TRACI-study integrating TWAS, GWAS, and eQTL analyses. We find the majority of P. falciparum parasites are transcriptomically converged within each geographic site with two broader physiological profiles across the Greater Mekong Subregion (GMS). We report 8720 SNP-expression linkages in the eastern GMS parasites and 4537 in the western. The minimal overlap between them suggests differential gene regulatory networks facilitating parasite adaptations to their unique host environments. Finally, we identify two genetic and physiological backgrounds associating with artemisinin resistance in the GMS, together with a farnesyltransferase protein and a thioredoxin-like protein which may act as vital intermediators linking the Pfk13 C580Y mutation to the prolonged parasite clearance time.

Suggested Citation

  • Lei Zhu & Jaishree Tripathi & Frances Maureen Rocamora & Olivo Miotto & Rob Pluijm & Till S. Voss & Sachel Mok & Dominic P. Kwiatkowski & François Nosten & Nicholas P. J. Day & Nicholas J. White & Arj, 2018. "The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07588-x
    DOI: 10.1038/s41467-018-07588-x
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    Cited by:

    1. Sourav Nayak & Thomas J. Peto & Michal Kucharski & Rupam Tripura & James J. Callery & Duong Tien Quang Huy & Mathieu Gendrot & Dysoley Lek & Ho Dang Trung Nghia & Rob W. Pluijm & Nguyen Dong & Le Than, 2024. "Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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