| Project/Area Number |
20K15789
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Lu Shiou-Ling 大阪大学, 大学院歯学研究科, 助教 (80830083)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 化膿レンサ球菌 / マクロファージ / Rab32 / Rab38 / microautophagy / Group A Streptococcus / Macrophage |
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| Outline of Research at the Start |
Macrophage engulf bacteria into lysosome for digestion. Phagocytosis and macroautophagy could be the pathways for go to lysosome. Bacteria evaded into cytoplasm could be captured by macroautophagy. In macrophage, lysosome membrane is more dynamic which change shape along with a big cargo directly: lysosome protrusion, as the lysosome wrapping mechanism (LWM) of microautophagy. I assume microautophagy is also potentially involved in GAS killing by lysosome in macrophage. Furthermore, I will see Rab32/Rab38 involved in the pathway through KO mouse and isolated cells.
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| Outline of Final Research Achievements |
Macrophages are professional phagocytes that engulf bacteria into lysosomes for digestion. Group A Streptococcus (GAS) can evade into the cytoplasm and are captured by macroautophagy. However, I found that only a small portion of GAS was surrounded by autophagosomes, even though most of the GAS population was suppressed in cells. In macrophages, I observed that small GTPase Rab32/38-associated lysosome-related organelles (LROs) present a structure resembling lysosome protrusion, a lysosome wrapping mechanism (LWM) recognized as microautophagy. I contributed to the completion of two papers identifying the role of Rab32/38-LRO in macrophages and osteoclasts, published in 2023. Continuing this project, I discovered that Rab32/38-LROs surround most intracellular GAS and are required for GAS clearance in macrophages, independent of macroautophagy
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| Academic Significance and Societal Importance of the Research Achievements |
化膿レンサ球菌（Group A Streptococcus, GAS）は、猩紅熱や壊死性筋膜炎、レンサ球菌性敗血症候群など幅広い疾患を引き起こす病原体で、過去20年でその毒性と感染症状が増強している。特に、昨年2023年から日本国内で劇症型溶血性レンサ球菌感染症の増加が報告されている。現在、適切なワクチンが存在せず、GASの病原性メカニズムを理解することが急務である。GAS感染では、ほとんどの細菌は免疫細胞マクロファージによって除去される。本研究、マクロファージがGASを分解する一部詳細なメカニズムを解明し、劇症型疾患の発症を抑制すること、例えば、敗血症に対する治療法の開発にヒントを提供する。
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