Identification of immunomodulation molecules in Mycobacterial ESX secretory systems

Research Project

Project/Area Number	18K15161
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 49050:Bacteriology-related
Research Institution	公益財団法人結核予防会結核研究所
Principal Investigator	Guo Tz-Chun 公益財団法人結核予防会結核研究所, 生体防御部病理科, 研究員 (00813065)
Project Period (FY)	2018-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	結核菌 / PPE遺伝子 / 病原体宿主相互作用 / 宿主自然免疫 / Mycobacteria / Immunomodulation / Dual RNAseq / Tuberculosis / ESX system
Outline of Final Research Achievements	Mycobacteria infection in host cells triggers a dynamic cascade of altered gene expression in both interacting organisms. To elucidate the functional role of ESX-5 secreted PE/PPE proteins in tuberculosis, two BCG deletion mutants, ppe26 or ppe27, were generated by mutagenesis. Macrophage cells were subjected to infection with wild-type and two mutated BCG variants. Dual RNA-seq was performed to unveil the altered gene expression both in the bacteria and infected host cells. Released cytokines were measured by multiplexed bead-based cytokine assay. The overall results from this study suggested the immunosuppressive role of PPE26 and PPE27. This confers the opportunity of manipulating PPE26/27 protein as potential candidate for drug intervention or vaccine development.
Academic Significance and Societal Importance of the Research Achievements	世界保健機関の2017年の推計では、世界の新規結核発症者は年間1000万人、結核による死者 (HIV陽性者を除く) は年間130万人とされており、結核制圧のための革新的な対策が必要とされている。今回、宿主と菌の相互作用を検討する過程で見出された宿主免疫応答を調節するPPE26, PPE27は、新たな診断、治療薬、ワクチンの開発にとって重要な分子として期待される。。