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

Shiroh Iwanaga (), Rie Kubota, Tsubasa Nishi, Sumalee Kamchonwongpaisan, Somdet Srichairatanakool, Naoaki Shinzawa, Din Syafruddin, Masao Yuda and Chairat Uthaipibull
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Shiroh Iwanaga: 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

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33804-w

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