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Genome-wide functional screening of drug-resistance genes in Plasmodium falciparum

Author

Listed:
  • Shiroh Iwanaga

    (Osaka University
    Osaka University)

  • Rie Kubota

    (Tokyo Medical and Dental University)

  • Tsubasa Nishi

    (Mie University)

  • Sumalee Kamchonwongpaisan

    (National Science and Technology Development Agency)

  • Somdet Srichairatanakool

    (Chiang Mai University)

  • Naoaki Shinzawa

    (Tokyo Medical and Dental University)

  • Din Syafruddin

    (Eijkman Institute for Molecular Biology)

  • Masao Yuda

    (Mie University)

  • Chairat Uthaipibull

    (National Science and Technology Development Agency
    Thailand Center of Excellence for Life Science)

Abstract

The global spread of drug resistance is a major obstacle to the treatment of Plasmodium falciparum malaria. The identification of drug-resistance genes is an essential step toward solving the problem of drug resistance. Here, we report functional screening as a new approach with which to identify drug-resistance genes in P. falciparum. Specifically, a high-coverage genomic library of a drug-resistant strain is directly generated in a drug-sensitive strain, and the resistance gene is then identified from this library using drug screening. In a pilot experiment using the strain Dd2, the known chloroquine-resistant gene pfcrt is identified using the developed approach, which proves our experimental concept. Furthermore, we identify multidrug-resistant transporter 7 (pfmdr7) as a novel candidate for a mefloquine-resistance gene from a field-isolated parasite; we suggest that its upregulation possibly confers the mefloquine resistance. These results show the usefulness of functional screening as means by which to identify drug-resistance genes.

Suggested Citation

  • Shiroh Iwanaga & Rie Kubota & Tsubasa Nishi & Sumalee Kamchonwongpaisan & Somdet Srichairatanakool & Naoaki Shinzawa & Din Syafruddin & Masao Yuda & Chairat Uthaipibull, 2022. "Genome-wide functional screening of drug-resistance genes in Plasmodium falciparum," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33804-w
    DOI: 10.1038/s41467-022-33804-w
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    1. Malcolm J. Gardner & Neil Hall & Eula Fung & Owen White & Matthew Berriman & Richard W. Hyman & Jane M. Carlton & Arnab Pain & Karen E. Nelson & Sharen Bowman & Ian T. Paulsen & Keith James & Jonathan, 2002. "Genome sequence of the human malaria parasite Plasmodium falciparum," Nature, Nature, vol. 419(6906), pages 498-511, October.
    2. Frédéric Ariey & Benoit Witkowski & Chanaki Amaratunga & Johann Beghain & Anne-Claire Langlois & Nimol Khim & Saorin Kim & Valentine Duru & Christiane Bouchier & Laurence Ma & Pharath Lim & Rithea Lea, 2014. "A molecular marker of artemisinin-resistant Plasmodium falciparum malaria," Nature, Nature, vol. 505(7481), pages 50-55, January.
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