| Project/Area Number |
18K19643
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中田 匡宣 大阪大学, 歯学研究科, 准教授 (90444497)
住友 倫子 大阪大学, 歯学研究科, 講師 (50423421)
山口 雅也 大阪大学, 歯学研究科, 助教 (00714536)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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| Keywords | レンサ球菌 / 細菌性髄膜炎 / 肺炎球菌 / 血液脳関門 |
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| Outline of Final Research Achievements |
Bacterial meningitis is considered to be caused by bacteremia, and then leads to blood-brain barrier disruption and dissemination of bacteria into the central nervous system. To investigate the mechanism by which Streptococcus pneumoniae, a colonizer of the nasopharynx, spreads to brain tissue, we utilized strain EF3030, clinically isolated from otitis media, for construction of a murine infection model. While neither bacteremia nor pneumonia was observed in this model, pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum. Notably, deletion of the ply gene encoding pneumolysin markedly compromised the ability of the organisms to disseminate into brain tissue. Taken together, our findings indicate that pneumolysin allows S. pneumoniae to disseminate from the nasopharynx into brain tissue in a non-hematogenous manner via the olfactory nerve pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
細菌性髄膜炎の治療では，髄液移行性が高い抗菌薬の静脈内投与が推奨されている．しかし，致死率や後遺症発生率は依然として高い．本研究では，鼻腔内に定着した肺炎球菌が嗅神経経路を介して脳組織へ非血行性に伝播する現象を証明した．本研究成果は，抗菌薬投与方法の見直しや鼻粘膜投与型ワクチンの開発など，細菌性髄膜炎の発症機構に基づく予防・治療法の提案につながると考える．
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