2022 Fiscal Year Final Research Report
Involvement in the pathogenic mechanism of Streptococcus pyogenes-derived extracellular vesicles
| Project/Area Number |
20K07495
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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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| Review Section |
Basic Section 49050:Bacteriology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
菊地 泰生 宮崎大学, 医学部, 准教授 (20353659)
相川 知宏 京都大学, 医学研究科, 助教 (70725499)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 細胞外小胞 / A群レンサ球菌 |
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| Outline of Final Research Achievements |
Most bacteria naturally release spherical lipid-bilayered extracellular vesicles (EVs) containing proteins, nucleic acids, and virulence-related molecules, thus contributing to diverse biological functions including transport of virulence factors. The proteome profile in this study revealed that GAS EVs enclosed many virulence-related proteins such as streptolysin O and NAD-glycohydrolase, facilitating their pathogenicity, and invasive GAS EVs were more abundant than non-invasive counterparts. Also, invasive GAS EVs showed slo-dependent cytotoxic activity and the induction of cytokine expression, contributing to GAS pathogenicity directly. Although non-invasive GAS EVs did not show cytotoxic activity, they may be utilized as a means to prevent antibacterial mechanisms such as autophagy, leading to enhancement of their own survival in the intracellular environment after the infection. Our findings indicate that EVs could be a key factor for GAS pathogenicity in GAS-host interactions.
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| Free Research Field |
細菌学
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| Academic Significance and Societal Importance of the Research Achievements |
EVsは多様な病原因子のデリバリーシステムとして機能し、細菌の感染戦略や病原性発揮の観点からも非常に重要な因子であると考えられているものの、その産生機構や宿主側との相互作用については、未だ不明な点が多い。そのため、EVsが直接的な病原性発揮機構の一つであることが明らかになれば、本研究の学術的意義は非常に大きい。さらに、EVsはワクチンとして利用することも可能である。近年、抗生物質耐性菌の増加など、細菌感染症に対する治療法の開発が急務であり、本研究による成果は、EVのワクチン応用のための効果的な利用法につながり、ワクチン開発における発展的な研究の一端になりうるため、社会的意義は高いと考えられる。
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