2018 Fiscal Year Final Research Report
Development of species-specific anti-bacterial therapeutic agents based on molecular interaction
| Project/Area Number |
17K19552
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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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| Research Field |
Pathology, Infection/Immunology, and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
津本 浩平 東京大学, 大学院工学系研究科(工学部), 教授 (90271866)
長門石 曉 東京大学, 医科学研究所, 特任准教授 (30550248)
相川 知宏 京都大学, 医学研究科, 助教 (70725499)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Keywords | A群レンサ球菌 / 鉄獲得系 / Shr / ヘム鉄 |
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| Outline of Final Research Achievements |
Streptococcus pyogenes, an important pathogen that causes a wide range of diseases, possesses the sia gene cluster, which encodes proteins involved in the heme acquisition system. Although this system was previously described, the molecular mechanism of effective heme transfer remains to be elucidated. Here, we have characterized the interactions between heme and each domain of Streptococcal hemoprotein receptor (Shr) and Streptococcal heme-binding protein (Shp). Our kinetic and thermodynamic analyses suggested that effective heme transfer within this system is achieved not only by affinity-based transfer but also by the difference of the binding driving force. The biophysical characterization of the above-mentioned interaction will lead to an indication for the selection of the target for a chemical screening of inhibitors as novel antibacterial agents based on biophysical approaches.
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| Free Research Field |
細菌学
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| Academic Significance and Societal Importance of the Research Achievements |
これまでの細菌感染の最も効果的かつ世界的に使用されている抗菌剤は，天然にある抗生物質を基本として修飾を加えたものや完全に合成された化学物質が使用されている．そのほとんどは、細菌が共通して保持する基本代謝の阻害活性に基づいているため菌種への特異性は低く、また耐性が獲得された場合には奏功しなくなる．本研究では、菌種に特異的な分子と生体側の分子との相互作用の阻害活性を持つ分子をスクリーニングできる大規模かつ効率的なin vitroのスクリーニング系を構築して，創薬シーズ基盤を構築することに挑戦的研究としての意義がある．
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