バクテリアの多剤耐性を克服する合成抗生物質

Matthew J Mitcheltree¹, Amarnath Pisipati¹, Egor A Syroegin²

¹Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

Nature

|October 28, 2021

まとめ

新しい合成抗生物質であるイボクサミシンは既存の薬に耐性のある菌株を含む抗生物質耐性細菌に対して特別な効能を示していますこの発見は抗生物質耐性との闘いにおいて新しい有望な武器をもたらします

科学分野:

薬剤化学
分子生物学
薬物の発見

背景:

抗生物質耐性菌の増加は世界的に深刻な健康上の脅威となっています
抗生物質の伝統的な半合成は進化する耐性に対処する上で限界があります
完全に合成された経路は新種の抗菌剤の設計により大きな柔軟性をもたらします

研究の目的:

抗生物質の新型構造を設計し合成する
新しい抗生物質の作用の構造的根拠を調査する
新型抗生物質の有効性と安全性を臨床前モデルで評価する.

主な方法:

オクセパノプロリン製の頑丈な支架を構造的に設計する.
新しい抗生物質イボクサミシンの合成
抗生物質とリボソームの複合構造を決定するX線結晶学.
細菌感染のマウスモデルでのin vivo有効性試験

主要な成果:

イボクサミシンは,ERMおよびCfr耐性メカニズムを持つ株を含むESKAPE病原体に対して強力な活性を示します.
構造研究により,イボキシミシンが細菌のリボソームに結合し,鍵となる核酸を異動させることが明らかになった.
イボクサミシンは,経口生物利用可能であり,マウスのグラム陽性およびグラム陰性感染症の両方の治療に有効です.
合成アプローチは伝統的な半合成の限界を克服します.

結論:

化学合成により,耐性菌株に対する広範囲の活性を持つ新種の抗生物質が作られます.
イボクサミシンは臨床応用の可能性のある新種の抗生物質です
この発見は,抗菌剤耐性との闘いにおける合理的な薬剤設計の重要性を強調しています.

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