Elucidation of the role of ferredoxin mutations in artemisinin resistance in malaria parasites

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06557
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Yamaguchi University
• Principal Investigator: Kimata Yoko 山口大学, 大学院創成科学研究科, 教授 (60255429)
• Co-Investigator(Kenkyū-buntansha): 齊藤 貴士 北海道科学大学, 薬学部, 准教授 (00432914) ; 小崎 紳一 山口大学, 大学院創成科学研究科, 教授 (40280581)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: マラリア原虫 / 薬剤耐性 / フェレドキシン

Outline of Final Research Achievements

Malaria is caused by malaria parasites that infect the body through mosquitoes. Artemisinin is a special drug for this purpose, but in recent years malaria parasites that are resistant to this drug have emerged, posing a serious problem. Mutations in an electron transport protein called ferredoxin, which malaria parasites have, have been reported to be one of the causes of resistance. In this study, we prepared this mutant ferredoxin protein and found that there were significant changes in protein functions such as the affinity and electron transfer rate of ferredoxin with the enzymes that donates and/or accepts electrons (FNR). Based on these results, we proposed a mechanism in which mutations in ferredoxin cause drug resistance by affecting various oxidative stress responses controlled by ferredoxin and related enzymes.

Free Research Field

生体分子科学

Academic Significance and Societal Importance of the Research Achievements

マラリア原虫の生化学的研究は、設備や培養材料の制約から限られており、アルテミシニンの標的や作用機序についてもごく少数例の報告しかない。本研究では、代表者らがこれまで蓄積してきた植物のフェレドキシンの生化学、物理化学、構造生物学的な知見や手法を用いて、マラリア原虫フェレドキシンが関与するアルテミシニン耐性の仕組みを提唱した。この仕組みの解明は、アルテミシニン耐性原虫の出現や拡散を抑制し、マラリア根絶を進めるための重要な情報を提供できると考える。