Elucidation of Molecular Mechanism of Mycobacterial Latency via Mycobacterial Membrane Vesicles

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16651
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: National Institute of Infectious Diseases (2021-2022); Osaka City University (2019-2020)
• Principal Investigator: Yamaguchi Takehiro 国立感染症研究所, 細菌第一部, 主任研究官 (40726080)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 結核 / メンブレンヴェシクル

Outline of Final Research Achievements

Tuberculosis (TB), one of the oldest infectious diseases known to mankind, still claims 1.4 million lives annually and causes tremendous damage. One of the factors that make the eradication of TB difficult is the unique properties of the causative agent, Mycobacterium tuberculosis (Mtb), such as dormancy and latency in the host. Here, we investigated the role of mycobacterial membrane vesicles (MVs), the extracellular vesicles from bacteria, in latency of Mtb. By creating recombinant bacteria, we attempted to identify the regulators of MV production. On the other hand, we also analyzed the impact of MV on host immunity. It became clear that the immunostimulatory activity and immunogenicity of MVs changed significantly depending on the culture conditions of MV-donor cells. Furthermore, the possibility of developing a novel vaccine against TB using mycobacterial MVs was demonstrated.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本邦での新規登録結核患者数は減少傾向にあるが、全世界的にはアジア・アフリカ・南米を中心に、結核はいまだに猛威をふるっている。新規抗結核薬の開発などにより結核死亡者数は減少傾向にあるものの、HIV陽性患者における結核死、多剤耐性結核の発生は増加しており、結核の撲滅には依然として解決すべき課題が山積している。
ウシ型結核菌弱毒株BCGワクチンは唯一確立された結核予防法であるが、その有効性は小児期に限られること、時にBCG感染症の副作用が出現することなど、問題点も指摘されている。
抗酸菌由来の膜小胞の新規結核ワクチンへの応用は、結核制御への新たなアプローチとなりうる。