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Genome-wide functional screening of drug-resistance genes in Plasmodium falciparum
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Document Title
Genome-wide functional screening of drug-resistance genes in Plasmodium falciparum
Author
Iwanaga S, Kubota R, Nishi T, Kamchonwongpaisan S, Srichairatanakool S, Shinzawa N, Syafruddin D, Yuda M, Uthaipibull C
Name from Authors Collection
Affiliations
Osaka University; Osaka University; Tokyo Medical & Dental University (TMDU); Mie University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Chiang Mai University; Eijkman Institute
Type
Article
Source Title
NATURE COMMUNICATIONS
Year
2022
Volume
13
Issue
1
Open Access
gold, Green Published
Publisher
NATURE PORTFOLIO
DOI
10.1038/s41467-022-33804-w
Format
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.
Funding Sponsor
Japan Society for the Promotion of Science [20H03477, 19K22527, 18K07084, 21K06985, 17H01542]; Japan Agency for Medical Research and Development (AMED) [21jm0210061h0004, 21wm0325018, 21wm0225014]
License
CC BY
Rights
Authors
Publication Source
WOS