| Project/Area Number |
16K08771
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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 |
Bacteriology (including mycology)
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| Research Institution | Chiba University |
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Principal Investigator |
Shimizu Takeshi 千葉大学, 大学院医学研究院, 准教授 (70312840)
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| Co-Investigator(Kenkyū-buntansha) |
野田 公俊 千葉大学, 大学院医学研究院, 教授 (60164703)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 腸管出血性大腸菌 / 一酸化窒素 / NO消去酵素 / 一酸化窒素還元酵素 / 病原性 / NOセンサー / 重症化 / NO還元酵素 |
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| Outline of Final Research Achievements |
This study aimed to reveal the cooperative roles of these defensive enzymes in EHEC against the nitrosative stress, NorV, Hmp and Hcp. Under anaerobic conditions, combined deletion of these enzymes significantly increased the NO-sensitivity of EHEC determined by the growth at 18 h; however, the norV-expression restored the NO-resistance of EHEC. On the other hand, the growth of the hmp mutant EHEC was inhibited after 6 h, indicating that NorV and Hmp play a cooperative role in anaerobic growth. Under microaerobic conditions, the growth of the hmp mutant EHEC was inhibited by NO, indicating that Hmp is the enzyme protect cells from NO stress under microaerobic condition. When EHEC was exposed to a lower concentration of NO, the NO level in bacterial cells of the hcp mutant EHEC was higher than those of the other deficient EHEC, suggesting that Hcp is solely effective in regulating NO levels at a low concentration.
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| Academic Significance and Societal Importance of the Research Achievements |
生体防御機構のうち殺菌物質の一つとして貪食細胞が産生するNOが知られており、EHECを含む大腸菌にはNOを消去する酵素を保持している。したがって、この産生された殺菌物質であるNOを消去できたら、生体防御機構を弱体化することができ、このことが高い病原性と関係していた。本研究成果ではEHECの保持するNO消去酵素のうち生体防御機構の効果を効果的に減少させているNO消去酵素を特定しており、この酵素の活性を阻害する阻害剤はEHECの予防薬や治療薬の用いることができると思われる。本研究成果はEHEC感染症の治療薬の標的酵素の一つを明らかにしたことに大きな意義がある。
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