| Project/Area Number |
17K15697
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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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 |
Hashino Masanori 国立感染症研究所, 病原体ゲノム解析研究センター, 研究員 (30783633)
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Streptococcus / 7型分泌装置 / 膿瘍形成 / 細菌毒素 / 細菌 / 感染症 |
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| Outline of Final Research Achievements |
Streptococcus intermedius TYG1620 strain was isolated as the causative agent from a brain abscess in an infant. In this study, to characterize the roles of Type 7 Secretion System (T7SS) in S. intermedius TYG1620 strain pathogenicity, we performed HeLa cell cytotoxicity assay, secretome analysis and transcriptome analysis using culture supernatant of clinical isolate TYG1620 and the transposon (Tn) mutant carrying Tn-insertion on essA (Tn-essA mutant) or essC (Tn-essC mutant) genes which is component of T7SS.
Ultrafiltrated TYG1620 culture supernatant exhibited T7SS-dependent cytotoxicity to HeLa cell. Secretome analysis revealed that several proteins exhibited marked decrease in both Tn-mutants compared with parent strain TYG1620. In addition, transcriptome analysis of HeLa cell treated with ultrafiltrated TYG1620 culture supernatant suggested that T7SS-dependent cytotoxicity was caused by cell membrane damage.
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| Academic Significance and Societal Importance of the Research Achievements |
脳膿瘍、肝膿瘍の原因菌であるStreptococcus intermedius (Si)の病原性には、未解明な部分が多い。本研究ではSi TYG1620株が上皮細胞に対するT7SS依存的な傷害性を保有することを見出した。さらに、実施したSecretome解析からT7SS依存的細胞傷害性は、これまでに報告のある病原因子と異なる因子に起因することが強く示唆された。つまり、本研究成果はSiの既知の病原因子ではなく、T7SS依存的新規病原因子の存在を示唆するものであり、Siの病原性および病態誘導機序の解明に重要な知見となることが十分に期待される。
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