Analysis of molecular mechanism concerning pneumococci-host interaction targeting for development for nex.t-generation pneumococcal vaccine

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08800
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: OGAWA MICHINAGA 国立感染症研究所, 細菌第一部, 室長 (80361624)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 肺炎球菌 / オートファジー

Outline of Final Research Achievements

In this study, we aimed to develop a new therapeutic method against Streptococcus pneumoniae, and conducted an analysis focusing on the interaction between pneumococcal virulence factor and the host factor. As a result, FIP200-independent LAPosome (LC3-associated phagosomes)-like vesicles (PcLV) were transiently induced after 1 h of infection, and FIP200-dependent bactericidal autophagy (PcAV) was subsequentially occurred after 2 h of infection. Furthermore, it was revealed that PcLV induction is prerequisite for PcAV induction, PcLV induction requires p62, NDP52, and Atg16L1 WD domain, and PcAV induction requires p62, Golgi-localized Rab41, and K63-linked poly-Ub chain formation by Nedd4-1.

Free Research Field

病原細菌学、細胞生物学、感染生物学

Academic Significance and Societal Importance of the Research Achievements

肺炎球菌は鼻咽頭に常在し、小児や高齢者では菌血症・髄膜炎といった致死性の高い侵襲性肺炎球菌感染症を引き起こす。近年、血清型交代によるワクチンが効かない血清型の肺炎球菌や、多剤耐性肺炎球菌の分離例が増加しており、新規治療法の開発が喫緊の課題である。本研究により、一次バリアである粘膜上皮細胞内での感染成立に必要な病原因子、菌の排除に必要な宿主細胞内での膜輸送系、さらには菌と宿主細胞との相互作用の一端が明らかとなり、新規治療法開発の標的分子探索に必要な基礎的な知見を多く得ることが出来た。今後、本研究をさらに発展させ、肺炎球菌と宿主との相互作用全体を俯瞰するモデルを構築していきたいと考えている。