Regulation of amyloidogenic biofilm-matrix formation
| Project/Area Number |
18KK0429
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied microbiology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
SUGIMOTO SHINYA 東京慈恵会医科大学, 医学部, 准教授 (60464393)
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| Project Period (FY) |
2019 – 2022
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
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| Keywords | バイオフィルム / マトリクス / 細胞外アミロイド / Curli / 大腸菌 / プロテアーゼ / 分子シャペロン / ペリプラズム / アミロイド / 菌体外マトリクス / Tail-specificプロテアーゼ / Prc / 作用機序 / ネガティブ・フードバック / 細胞外小胞 / アミロイド線維 |
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| Outline of Final Research Achievements |
Enteric bacteria synthesize extracellular functional amyloids, curli, during biofilm formation and host colonization. Although aggregation of the major curli subunit, CsgA, is prevented by cytoplasmic and periplasmic molecular chaperones, its degradation in cells remains unclear. Here, using genomically engineered E. coli and multicopy-suppressor screening, we discovered that serine proteases Prc is involved in degradation of CsgA in the periplasm. Expression of the csg operon is down-regulated at the transcription level under the situations where CsgA aggregates could accumulate in the periplasm. In addition, production of extracellular membrane vesicles was stimulated under the similar situations. Furthermore, we proposed functional hierarchy of J-domain proteins that work with molecular chaperone DnaK in regulation of curli biosynthesis.
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| Academic Significance and Societal Importance of the Research Achievements |
地球上の微生物の大部分は固体表面に付着し、自身が産生するマトリクス（多糖・核酸・タンパク質・アミロイド線維など）に覆われながら“バイオフィルム”と呼ばれる集合体を形成して生息している。バイオフィルムが生体内や体内留置型医療デバイスの表面に作られると、バイオフィルム中の菌は抗菌薬や宿主免疫に抵抗性を示すため、難治性感染症の原因になる。本研究で得られた成果は、このようなバイオフィルムに関連した感染症の治療法・予防法の開発に繋がる可能性がある。
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Report
(2 results)
Research Products
(2 results)
