| Project/Area Number |
15K09575
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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 |
Infectious disease medicine
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| Research Institution | Nagoya City University |
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Principal Investigator |
Tatsuno Ichiro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (50311642)
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| Co-Investigator(Kenkyū-buntansha) |
長谷川 忠男 名古屋市立大学, 医薬学総合研究院(医学), 教授 (10314014)
井坂 雅徳 名古屋市立大学, 医薬学総合研究院(医学), 助教 (40336673)
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| Project Period (FY) |
2015-04-01 – 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 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | A群レンサ球菌 / 病原性 / ゲノム / fabT / Ａ群レンサ球菌 / 二成分制御系 / streptococcus / pyogenes / NADase / 劇症型感染症 / S. pyogenes / Sreptococcus / mefA / salR / salK / msrD / fab |
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| Outline of Final Research Achievements |
Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Recently, we showed that the regions encoding the SalR-SalK, a two-component regulatory system, were deleted in some emm 1-type isolates (named as “novel-type”). In this study, the two novel “STSS” isolates 10-85 and 11-171 were more virulent than the two novel “non-STSS” isolates 11O-2 and 11T-3 when examined using a mouse model of invasive infection. Genome sequencing experiments using the three strains 10-85, 11-171, and 11O-2 detected only one single nucleotide polymorphism that causes a non-synonymous mutation in fabT encoding a transcriptional regulator in strain 11O-2. Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non-STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O-2, suggesting that the mutation in fabT is involved in the differential virulence among the novel-type clinical isolates.
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| Academic Significance and Societal Importance of the Research Achievements |
A群レンサ球菌新型株（特徴として、SalR-SalK遺伝子を含む領域を欠損している）には病原性の高い株と病原性の低い株の２種類が存在する。この病原性の違いが、fabT遺伝子の変異に依存していることを突き止めた。fabT遺伝子に変異を持つ株が一定の割合で出現することは、海外のグループからも報告された。しかし、病原性が低下するようなfabT遺伝子の変異が自然界で起こる理由についてはいまだ不明である。
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