Identification of drug resistant genes against partner drugs of ACT

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04071
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Shiroh Iwanaga 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20314510)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: マラリア / 薬剤耐性

Outline of Final Research Achievements

Global spread of drug-resistant Plasmodium falciparum is a major obstacle to malaria treatment. Although the identification of drug resistance genes is crucial to efforts aimed at fighting resistant parasites, no effective approach has yet been developed. Here, we report genome-wide functional screening as a new approach to identify drug resistance genes in P. falciparum: genomic libraries of a drug-resistant strain are directly generated in drug-sensitive parasites and the drug resistance gene is then robustly identified from these libraries by drug screening. We successfully used this approach to identify multi-drug-resistant transporter 7, an ATP-binding cassette transporter, as a novel mefloquine resistance gene from a field-isolated parasite strain, thus demonstrating the practical utility of the method. Genome-wide functional screening will facilitate the identification of drug resistance genes and will contribute to the global fight against drug-resistant parasites.

Free Research Field

寄生虫・衛生動物学

Academic Significance and Societal Importance of the Research Achievements

マラリア治療にはアルテミシニンとパートナー薬剤（メフロキン・ピペラキン）による併用療法（ACT)が用いられる。しかし現在、パートナー薬剤に対する耐性が蔓延しており、耐性を回避するパートナー薬剤の選択がACTの成否の鍵となっている。最適なパートナー薬剤を選択するためには耐性原虫の蔓延状況を正確に把握する必要がある。しかしピペラキンとは異なりメフロキン耐性原虫の蔓延状況は未だ正確に把握されていない。これに対し本研究の成果はメフロキン耐性を監視する絶対的な分子マーカー（耐性遺伝子）を与える。これにより正確な疫学調査に基づく最適なパートナー薬剤の選択が可能となり、成功率の高いACTを提供できる。