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多剤耐性病原体を標的とする自然に由来する抗生物質
Zongqiang Wang1, Bimal Koirala1, Yozen Hernandez1
1Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, USA.
Nature
|January 6, 2022
まとめ
新しい抗生物質であるマコラチンは コリスチンに抵抗する グラム陰性細菌と闘います Acinetobacter baumanniiのような 危険な病原体に対して効果があり 抗生物質耐性に対する 解決策となる可能性があります
科学分野:
- 微生物学
- 薬物の発見
- ゲノミクス
背景:
- 抗生物質耐性菌は 世界的に蔓延する健康問題です
- コリスチンは 重要な最後の抗生物質ですが 耐性が生まれています
- mcr-1遺伝子の拡散は コリスチンの有効性を著しく脅かしている.
研究 の 目的:
- 自然に発生するコリスチン共生物質を,mcr-1媒介による耐性に対する溶液に調べる.
- コリスチン耐性病原体に対して有効な新しい化合物を特定し合成する.
- 薬剤耐性の高いグラム陰性感染症の新たな治療法を開発する
主な方法:
- 関連する生物合成遺伝子クラスタを特定するために,細菌のゲノムをバイオ情報分析.
- コリスティンの同位体であるマコラシンの化学合成
- mcr-1と固有の耐性を含むグラム陰性病原体に対する in vitroおよびin vivo試験
- マウスの感染モデルにおけるマコラシンアナログの評価
主要な成果:
- 新しいコリスチン共生体であるマコラシンが特定され,合成された.
- マコラシンは,mcr-1 を発現するグラム陰性病原体に対する活性を示した.
- この化合物は,Acinetobacter baumanniiとNeisseria gonorrhoeaeを含む固有のコリスチン耐性細菌に対して有効でした.
- マコラシンの類型は,薬剤耐性の高いコリスチン耐性Acinetobacter baumanniiに対して,マウスモデルで有効性を示した.
結論:
- 自然に存在するコリスチン共生物質は 抗生物質耐性の発生に 解決策を提供することができます
- マコラシンは,コリスチン耐性グラム陰性感染症に対する有望な,自然にインスパイアされた治療薬である.
- この発見は 薬剤耐性の高いバクテリアが 引き起こす重大な脅威を克服する 戦略を提示しています
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