2023 Fiscal Year Annual Research Report
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.
| Project/Area Number |
20K15789
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
LU SHIOULING 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 | Group A Streptococcus / Macrophage / Rab32 / Rab38 |
|---|
| Outline of Annual Research Achievements |
In the pass year, I confirmed that in ATG7 knockout macrophages still maintained antibiotic activity, indicated that, macroautophage is not the major procedure for bacteria degradation. I further investigated whether microautophagy target GAS and whether Rab32/Rab38 is involved in this lysosome wrapping mechanism (LWM) by EM images analysis. The lysosome frequently shows a multi-layers in macrophage. Most of the lysosome containing GAS in wild type cells. Few cytosol GAS was observed. A clear lysosome elongation to cytosol GAS, lysosome protrusion, was found in wild type macrophages but not Rab32/38 DKO cells, implying Rab32/38 mediated microautophagy for partial GAS suppression.
In addition, our previous data had confirmed that Rab32/38 is required for lysosome-related organelle acidification. I found that, in GAS-infected Rab32/38 DKO cells, EM images showed a empty/lose space of GAS-containing phagosome, implying that Rab32/38 is required for phagosome/LC3-associated phagosome (LAP) function. Take together, in stead of macroautophagy, microautophagy and LAP, both involves Rab32 and Rab38 recruitment, are the major procedures for GAS clearance in macrophage.
Macrophage has been recognized as an important role for bacterial clearance, but in some case, somehow, bacteria can escape from intracellular degradation. Rab32/38 defective have show that Understand the molecular mechanism, provide by this research results, would help to have a better knowledge for development therapeutic strategy.
|
