Identification of drug resistant genes against partner drugs of ACT
| Project/Area Number |
17H04071
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Tokyo Medical and Dental University |
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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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | マラリア / 薬剤耐性 / メフロキン |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] CXCR4 regulates Plasmodium development in mouse and human hepatocytes2019
Author(s)
Bando Hironori、Pradipta Ariel、Iwanaga Shiroh、Okamoto Toru、Okuzaki Daisuke、Tanaka Shun、Vega-Rodr?guez Joel、Lee Youngae、Ma Ji Su、Sakaguchi Naoya、Soga Akira、Fukumoto Shinya、Sasai Miwa、Matsuura Yoshiharu、Yuda Masao、Jacobs-Lorena Marcelo、Yamamoto Masahiro
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Journal Title
J Exp Med.
Volume: 216
Pages: 1733-1748
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors2017
Author(s)
Saito Fumiji、Hirayasu Kouyuki、Satoh Takeshi、Wang Christian W.、Lusingu John、Arimori Takao、Shida Kyoko、Palacpac Nirianne Marie Q.、Itagaki Sawako、Iwanaga Shiroh、Takashima Eizo、Tsuboi Takafumi、Kohyama Masako、Suenaga Tadahiro、Colonna Marco、Takagi Junichi、Lavstsen Thomas、Horii Toshihiro、Arase Hisashi
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Journal Title
Nature
Volume: 552
Pages: 101-105
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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