Analysis of the role of pneumococcal interactions with glycosaminoglycans in the inflammatory response and establishment of infection
| Project/Area Number |
17K11666
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Osaka University |
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Principal Investigator |
Yujiro Hirose 大阪大学, 歯学研究科, 特任助教 (90788407)
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| Co-Investigator(Kenkyū-buntansha) |
山口 雅也 大阪大学, 歯学研究科, 助教 (00714536)
川端 重忠 大阪大学, 歯学研究科, 教授 (50273694)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺炎球菌 / 髄膜炎 / 脳微小血管内皮細胞 / 付着 / 侵入 / Ccs4 / 病原因子 / 糖鎖 / グリコサミノグリカン / 血液脳関門 / 付着・侵入 |
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| Outline of Final Research Achievements |
Streptococcus pneumoniae is a major pathogen that causes pneumonia and meningitis. Neisseria meningitidis, another pathogen causing meningitis, promotes the survival in human serum through an Arginine-rich region of its lipoprotein. S. pneumoniae competence-induced protein Ccs4 showed similarities with the Arginine-rich region.
We constructed ccs4 mutant strain of S. pneumoniae wild-type strain. The deletion of ccs4 decreased the adhesion and invasion against human brain microvascular endothelial cells. There were no significant differences between the survival rate of the ccs4 mutant and wild-type strains in mouse blood. In a mouse sepsis model, ccs4 mutant strain-infected mice showed a significantly prolonged survival time as compared to wild-type strain-infected mice.
These results indicated that Ccs4 is involved in pneumococcal adhesion to and invasion of host endothelial cells and contributed to the virulence of S. pneumoniae.
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| Academic Significance and Societal Importance of the Research Achievements |
肺炎球菌は口や喉から分離される病原菌である。全身に伝播した場合、髄膜炎や敗血症などの致死性が高い疾患を引き起こす。高齢者人口の増加や薬剤耐性菌の出現に伴い、肺炎球菌による感染症は社会的問題になっている。同菌に対しては、莢膜多糖を抗原とする多価ワクチンが使用されているが、免疫の持続時間や血清型のカバーなどの問題があり、新規治療法の開発が望まれている。
本研究では、肺炎球菌が髄膜炎発症に際して血液脳関門を突破するときに利用する新規分子として、形質転換誘導性タンパク質Ccs4を発見した。発症機構に関与する菌分子の同定は、予防効果の高い治療法の確立に道を開く可能性がある。
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Report
(4 results)
Research Products
(67 results)
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[Journal Article] Surface pre-reacted Glass filler contributes to tertiary dentin Formation through a Mechanism different than that of hydraulic calcium-silicate cement.2019
Author(s)
Okamoto M, Ali M, Komichi S, Watanabe M, Huang H, Ito Yuki, Miura J, Hirose Y, Mizuhira M, Takahashi Y, Okuzaki D, Kawabata S, Imazato S, Hayashi M.
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Journal Title
Journal of Clinical Medicine.
Volume: 8
Issue: 9
Pages: 11-11
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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