Molecular analysis for pathogenesis of SubAB produced by Enterohemorrhagic Escherichia coli through the inhibitory effects on host innate immunity
| Project/Area Number |
17K10019
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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 |
Infectious disease medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
Tsutsuki Hiroyasu 熊本大学, 大学院生命科学研究部(医), 助教 (40586608)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 腸管出血性大腸菌 / Subtilase cytotoxin / 自然免疫 / インフラマソーム / 小胞体ストレス / 宿主防御機構 / 細菌毒素 |
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| Outline of Final Research Achievements |
Subtilase cytotoxin (SubAB), a toxin produced by Enterohemorrhagic Escherichia coli, induces cytotoxicity through Endoplasmic reticulum (ER) stress. Here we investigated the molecular mechanisms of inhibitory effects of SubAB on host innate immunity. We found that SubAB inhibited IL-1β production and inflammasome activation in macrophages. As a result of mouse infection model, SubAB increased the number of pathogenic bacteria in mouse feces. These data suggested that SubAB enhance EHEC colonization through inhibition of host innate immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
腸管出血性大腸菌(EHEC)の主な病原因子は志賀毒素であり、血清型O157が最も知られているが、O111やO104など様々な血清型のEHECも集団食中毒を起こしている。近年、新たな毒素SubABを産生するO113などが臨床患者から検出される事例が増加している。これまでEHEC感染病態におけるSubABの役割は不明であり、制御法は開発されていない。本研究提案は、EHEC 感染病態におけるSubAB の役割を解明することで、新たな治療戦略の立案に役立つ。未知の炎症機構の発見にも繋がり、細菌学研究にとどまらず、病態生理・感染症学分野を含む臨床応用研究領域に全く新しい知見を与えることが期待される。
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Report
(4 results)
Research Products
(27 results)
