Study the mechanism how Rab32/Rab38 positive lysosome related organelle is involved in bacteria suppression through macroautophagy and microautophagy in macrophage and mouse infectious model.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K15789
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Osaka University
• Principal Investigator: Lu Shiou-Ling 大阪大学, 大学院歯学研究科, 助教 (80830083)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 化膿レンサ球菌 / マクロファージ / Rab32 / Rab38 / microautophagy

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

Free Research Field

細胞生物、細菌感染

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。