Analysis of molecular mechanism concerning pneumococci-host interaction targeting for development for nex.t-generation pneumococcal vaccine
| Project/Area Number |
16K08800
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
OGAWA MICHINAGA 国立感染症研究所, 細菌第一部, 室長 (80361624)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肺炎球菌 / オートファジー / FIP200 / 病原性 / 選択的オートファジー / カーゴレセプター / Rab41 / Nedd4-1 / メンブレントラフィック / 殺菌機構 / ワクチン |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(28 results)
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[Journal Article] Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination2018
Author(s)
Ogawa M, Matsuda R, Takada N, Tomokiyo M, Yamamoto S, Shizukusihi S, Yamaji T, Yoshikawa Y, Yoshida M, Tanida I, Koike M, Murai M, Morita H, Takeyama H, Ryo A, Guan JL, Yamamoto M, Inoue JI, Yanagawa T, Fukuda M, Kawabe H, Ohnishi M
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Journal Title
Cellular Microbiology
Volume: e12846
Issue: 8
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intracellular fate of Ureaplasma parvum entrapped by host cellular autophagy2017
Author(s)
Nishiumi F, Ogawa M, Nakura Y, Hamada Y, Nakayama M, Mitobe J, Hiraide A, Sakai N, Takeuchi M, Yoshimori T, Yanagihara I*
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Journal Title
MicrobiologyOpen
Volume: -
Issue: 3
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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