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

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21395
• Project/Area Number (Other): 18H06308 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0907:Oral science and related fields
• Research Institution: Osaka University
• Principal Investigator: Lu Shiou-Ling 大阪大学, 歯学研究科, 助教 (80830083)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 内皮細胞 / VEGF / 化膿レンサ球菌

Outline of Final Research Achievements

Group A streptococcus (GAS) is deleterious bacteria that causes life-threatening diseases including breakdown of blood vessel. Here, we explored a strategy how endothelial cells could defense against invaded GAS. Vascular endothelial growth factor (VEGF) promotes many diverse biological functions in endothelial cells. We found that supplement of VEGF significantly enhanced GAS clearance in endothelial cells. VEGF inactivated mTOR activity, which resulted in an activation of TFEB, a transcriptional factor crucial for lysosome/autophagy biogenesis. Xenophagy was also partially rescued in VEGF-treated endothelial cells. Furthermore, there is a low VEGF concentration existing in GAS-infected patient sera accompanied with serious disease symptom, such as sepsis also our animal infection model. These suggest endothelial cells are short of VEGF stimulation under GAS infectious condition. We aim to develop this finding toward a future clinical application.

Free Research Field

感染細胞生物

Academic Significance and Societal Importance of the Research Achievements

GAS bacteria causes life-threatening diseases. Patients are usually companion with body liquid lost and low blood pressure and shock, due to the blood vessel damage. Here, we provide a strategy for clinical therapy that VEGF may be an option for supplement with antibiotic treatment.