双重機能の抗生物質-トランスポーター結合体は,MRSAバイオフィルムを消毒し,持続細胞を殺すのに優れた活性を示しています
Alexandra Antonoplis1, Xiaoyu Zang1, Melanie A Huttner1
1Department of Chemistry , Stanford University , Stanford , California 94305 , United States.
Journal of the American Chemical Society
|November 3, 2018
まとめ
新しいバンコミシン-オクターギニン結合体 (V-r8) は,メチシリン耐性黄色のステーキ菌 (MRSA) のバイオフィルムと持続細胞を効果的に根絶しました. この有望な薬は抗生物質に不敏感なMRSA感染に対して強力な活性を示しています.
科学分野:
- 微生物学
- 感染症
- 薬物の発見
背景:
- メチシリン耐性黄色のステーキ菌 (MRSA) は,抗生物質耐性感染症による高い死亡率を引き起こし,世界的な健康上の重大な脅威となっています.
- 既存の治療法は バイオフィルムや持続性細胞のような 抗生物質に敏感でない細菌集団と 闘っています
研究 の 目的:
- 抗生物質に不敏感な形態を含むMRSAを標的とした新しい二重機能コンジュガットを開発し評価する.
- ヴァンコミシン-d-オクターギニン結合体 (V-r8) のMRSAに対する有効性を in vitroおよびin vivoで調査する.
主な方法:
- バンコミシン-d-オクターギニンの結合体 (V-r8) の設計と合成
- MRSAバイオフィルムと持続細胞に対するV-r8のインビトロ評価
- ネズミの創傷感染モデルにおけるV- r8の有効性のインビボ評価
- V-r8の細胞蓄積と膜干渉の性質の分析
主要な成果:
- V- r8はMRSAバイオフィルムと細胞を in vitroで根絶し,バンコミシンを大幅に上回った.
- V- r8は,ネズミの傷口感染モデルで,バイオフィルムに関連したMRSAの97%を排除した.
- 結合剤はバンコミシンと比較して細胞の蓄積と膜の乱れを強めた.
- V- r8で急性皮膚への毒性は観察されなかった.
結論:
- バンコミシン-d-オクターギニン結合体 (V-r8) は,抗生物質に不敏感なMRSAに対する強力な薬剤である.
- V- r8は,迅速かつ有効な作用により,臨床的なMRSA感染の治療に有望である.
- この二重機能のコンジュガートは MRSA感染に対する新しい戦略です
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