Elucidation of Molecular Mechanism of Mycobacterial Latency via Mycobacterial Membrane Vesicles
| Project/Area Number |
19K16651
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49050:Bacteriology-related
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| Research Institution | National Institute of Infectious Diseases (2021-2022)
Osaka City University (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 結核 / メンブレンヴェシクル / BCG / 宿主内潜伏 |
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| Outline of Research at the Start |
昨今、いずれの細菌種もタンパク質や脂質、核酸で構成される直径30-500 nmのメンブレンヴェシクル（MV）を産生することが分かってきた。一方で疾患起因性から重要な結核菌のMVには宿主免疫抑制的な作用があると報告されているが、その分子機序は全く解明されていない。結核菌は宿主細胞内で数十年にわたる潜伏を果たす特異な性質を有しているが、その過程にMVが関与している可能性が高い。そこで、本研究は抗酸菌のMV産生制御因子とMV中に存在する宿主免疫抑制因子を同定し結核菌MVの宿主細胞内潜伏に果たす役割の解明を目的とする。
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| 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.
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| 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。
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Report
(5 results)
Research Products
(31 results)
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[Journal Article] Lysocin E Targeting Menaquinone in the Membrane of Mycobacterium tuberculosis Is a Promising Lead Compound for Antituberculosis Drugs.2022
Author(s)
Geberetsadik G, Inaizumi A, Nishiyama A, Yamaguchi T, Hamamoto H, Panthee S, Tamaru A, Hayatsu M, Mizutani Y, Kaboso SA, Hakamata M, Ilinov A, Ozeki Y, Tateishi Y, Sekimizu K, Matsumoto S.
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Journal Title
Antimicrob Agents Chemother
Volume: 66
Issue: 9
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Direct attachment with erythrocytes augments extracellular growth of pathogenic Mycobacteria2022
Author(s)
Nishiuchi, Y., Tateishi, Y., Hirano, H., Ozeki, Y., Yamaguchi, T., Miki, M., Kitada, S., Maruyama, F., Matsumoto, S.
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Journal Title
Microbiology Spectrum
Volume: in press
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Soluble urokinase-type plasminogen activator receptor represents exercise tolerance and predicts adverse cardiac events in patients with heart failure.2020
Author(s)
Ishikawa H, Izumiya Y, Shibata A, Ichikawa Y, Yamaguchi T, Yamaguchi Y, Kitada R, Iwata S, Ehara S, Tomita S, Hanatani A, Yoshiyama M.
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Journal Title
Heart Vessels.
Volume: 35
Issue: 5
Pages: 681-688
DOI
NAID
Related Report
Peer Reviewed / Open Access
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