Study the antimicrobial activity of VEGF-TFEB for endothelial cells defense against group A streptococcus infection.

2019 Fiscal Year Annual Research Report

• Project/Area Number: 19K21395
• Allocation Type: Multi-year Fund
• Research Institution: Osaka University
• Principal Investigator: LU SHIOULING 大阪大学, 歯学研究科, 特任助教 (80830083)
• Project Period (FY): 2019-04-01 – 2020-03-31
• Keywords: Group A Streptococcus / VEGF / Endothelial cell / TFEB

Outline of Annual Research Achievements

The goal of this project is to clarify the mechanism of VEGF-TFEB mediated antimicrobial effects for endothelial cell defense against GAS infection. In 2019, I had completed specific aim 2 and specific aim 3.
last year, the results in the aim 1, I had found VEGF provide suppression effects for endothelial cell to again GAS. For specific aim 2, I demonstrated VEGF-mediated antimicrobial activity through TFEB activation. VEGF induces Ca2+release and partially affects mTORC1 activity. Ca2+ level was confirmed by Fluo8 stain. VEGF mediated TFEB nuclear trans-localization. Bacterial number was affected by TFEB overexpression or siRNA knockdown confirmed TFEB is required for GAS clearance. I also clarified that VEGF-mediated TFEB activation rescue xenophagy in endothelial cells. Since TFEB activation also increase autophagy, I detected autophagy related gene FIP200 recruitment on GAS-containing vesicles and found the efficiency was enhanced by VEGF. Most importantly, I found VEGF mediated a successful autophagosome, isolation membrane (IM), target on GAS under electron microscope observation. I concluded that VEGF-mediated TFEB activation could even more rescue xenophagy against GAS in endothelial cells.

Research Products

• [Int'l Joint Research] 国立成功大学医学大学院(台湾)
  • Country Name: その他の国・地域
  • Counterpart Institution: 国立成功大学医学大学院
• [Journal Article] Nicotinamide Increases Intracellular NAD+ Content to Enhance Autophagy-Mediated Group A Streptococcal Clearance in Endothelial Cells. (2020)
  • Author(s): Cheng-Lu Hsieh, Shu-Ying Hsieh, Hsuan-Min Huang, Shiou-Ling Lu, Hiroko Omori, Po-Xing Zheng, Yen-Ning Ho, Yi-Lin Cheng, Yee-Shin Lin, Chuan Chiang-Ni, Pei-Jane Tsai, Shu-Ying Wang, Ching-Chuan Liu, Takeshi Noda and Jiunn-Jong Wu.
  • Journal Title: Front. Microbiol. Volume: 11 Pages: 117
  • DOI: 10.3389/fmicb.2020.00117.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Group A Streptococcus Induces LAPosomes via SLO/β1 Integrin/NOX2/ROS Pathway in Endothelial Cells That Are Ineffective in Bacterial Killing and Suppress Xenophagy. (2019)
  • Author(s): Yi-Lin Cheng, Chih-Feng Kuo, Shiou-Ling Lu, Hiroko Omori, Ya-Na Wu, Cheng-Lu Hsieh, Takeshi Noda, Shang-Rung Wu, Robert Anderson, Chiou-Feng Lin, Chia-Ling Chen, Jiunn-Jong Wu, Yee-Shin Lin.
  • Journal Title: mBio Volume: 10 Pages: e02148-19
  • DOI: 10.1128/mBio.02148-19.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] VEGFに依存した血管内皮細胞における抗菌作用機序の解明 (2019)
  • Author(s): Shiou-Ling Lu, 大森弘子, Chao-Ping Liao, Yee-Shin Lin, Ching-Chuan Liu, 野田健司
  • Organizer: 第12回オートファジー研究会
• [Presentation] VEGF activates endo-lysosomal activity through mTORC1-TFEB pathway that suppresses Group A streptococcus infection in endothelial cells. (2019)
  • Author(s): Shiou-Ling Lu, Hiroko Omori, Chao-Ping Liao, Yee-Shin Lin, Ching-Chuan Liu, Takeshi Noda.
  • Organizer: 8th International Symposium on Autophagy (ISA), Taipei, Taiwan
  • Int'l Joint Research
• [Presentation] The mechanism of VEGF-mediated antimicrobial effects for endothelial cell defense against GAS infection. (2019)
  • Author(s): Shiou-Ling Lu, Hiroko Omori, Chao-Ping Liao, Yee-Shin Lin, Ching-Chuan Liu, Takeshi Noda.
  • Organizer: International Symposium of Infectious Disease, Tainan, Taiwan.
  • Int'l Joint Research
• [Presentation] 化膿レンサ球菌感染におけるVEGFに依存した抗菌作用の解明 (2019)
  • Author(s): Shiou-Ling Lu, Hiroko Omori, Chao-Ping Liao, Yee-Shin Lin, Ching-Chuan Liu, Takeshi NODA
  • Organizer: 日本分子生物学会
  • Invited