| Project/Area Number |
17K08344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Natural medicines
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| Research Institution | Kitasato University |
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Principal Investigator |
Mori Mihoko 北里大学, 感染制御科学府, 助教 (20425648)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Entamoeba histolytica / NAD kinase / 微生物二次代謝産物 / 天然化合物 / 赤痢アメーバ / アメーバ赤痢 / 微生物培養液 / 微生物代謝産物 / 化合物ライブラリー |
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| Outline of Final Research Achievements |
Amebiasis is a diarrheal disease in human, caused by infection with the protozoan parasite Entamoeba histolytica. Metronidazole has been a drug of choice against amebiasis for decades, however, this drug has several side effects and the resistant strain has been reported. Therefore, new drugs with different modes of action or targets have been needed. In this study, we established the screening system for inhibitors against E. histolytica NAD kinase. E. histolytica NAD kinase has the unique character and the essentiality of its gene has been confirmed. Although the screening for Eh NADK inhibitors was conducted using microbial broth extracts, no sample showed the inhibition. Concurrently we screened antiamebic samples using microbial broth extracts. We found chartreusin as an antiamebic compound with ED50 = 100 microM from a broth extract of one Streptomyces strain, and found tenuazonic acid as an antiamebic compound with ED50 = 50 microM from a broth extract of Aspergillus nomius.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において赤痢アメーバのNAD kinaseを阻害する微生物培養液を見出すことができなかった。評価法あるいは微生物培養液の調製法を見直す必要があると考えられた。並行して行った赤痢アメーバ原虫を用いた殺虫活性評価では複数の殺虫活性化合物が得られた。本研究において、赤痢アメーバ原虫の細胞選択的に毒性を示し、多くの種類の微生物が生産する化合物に関する知見を蓄積できた。今後の新規赤痢アメーバ症治療薬探索研究に活用されるよう本知見を論文として発表する。
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