FtsZの阻害剤で,強力で選択的な抗スタフィロコック性活性を持っています
David J Haydon1, Neil R Stokes, Rebecca Ure
1Prolysis, Begbroke Science Park, Oxfordshire OX5 1PF, UK.
Science (New York, N.Y.)
|September 20, 2008
まとめ
新しい合成抗菌剤PC190723は,感染と戦うためにFtsZ (細菌の細胞分裂における重要なタンパク質) を標的とする. この化合物は,薬剤耐性である黄金球菌 (Staphylococcus aureus) に対して強力な活性を示し,動物モデルでの有効性を示しています.
科学分野:
- 微生物学と分子生物学について
- 薬物の発見と開発
背景:
- FtsZは,細胞分裂に不可欠な重要な細菌のGTPaseであり,哺乳類のβ-チューブリンと同型である.
- FtsZをターゲットにすることは,新しい抗菌剤の開発のための潜在的な戦略を提供します.
研究 の 目的:
- FtsZを標的にする小型合成抗菌剤の可能性を調査する.
- PC190723の耐性菌株を含むStaphylococcus aureusに対する有効性を評価する.
主な方法:
- FtsZの合成小分子阻害剤の開発.
- スタフィロコーシに対する殺菌性のインビトロ評価.
- Staphylococcus aureus感染のマウスモデルにおけるin vivo有効性研究.
- FtsZ.の阻害剤結合部位のマッピング
主要な成果:
- PC190723は,メチシリン耐性菌株を含む,Staphylococcus aureusに対する強力な選択的インビトロ殺菌活性を示した.
- FtsZのPC190723の結合部位は,tubulin.onのTaxol結合部位に類似して特定されました.
- PC190723は,Staphylococcus aureusの致死量に感染したマウスを成功裏に治した.
結論:
- FtsZは,抗菌薬の開発のための実行可能なターゲットとして検証されています.
- PC190723は,新型の抗スタフィロコックスの治療法を開発するための主要な化合物として有望であることを示しています.
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