エッセンシャル・リボスイッチの阻害によって活性化するグラム陰性抗生物質
Stephen E Motika, Rebecca J Ulrich, Emily J Geddes
1Department of Pathobiology, University of Illinois, Urbana, Illinois 61802, United States.
Journal of the American Chemical Society
|May 21, 2020
まとめ
研究者は抗生物質リボシールCを 多剤耐性グラム陰性感染症に効果的に標的として変えました この発見により 細菌の蓄積が大きくなり 難しい感染症の治療策が生まれました
科学分野:
- 微生物学
- 薬物の発見
- 抗菌剤に対する耐性
背景:
- 多剤耐性グラム陰性感染症は,治療の選択肢が限られているため,世界的な健康上の重大な脅威となっています.
- 新しい抗生物質の開発は,グラム陰性細菌内の化合物の蓄積が悪いため困難です.
研究 の 目的:
- 抗生物質リボシールCを設計して グラム陰性病原体に対する蓄積と有効性を高める
- グラム陰性細菌に対するフラビンモノヌクレオチド (FMN) リボスイッチ結合剤のトランスレーション可能性を評価する.
主な方法:
- エシェリキア・コリ菌における化合物蓄積の予測ガイドラインを使用した.
- 改造されたリボシルCは,グラム陰性細菌に浸透し蓄積する能力を向上させる.
- グラム陰性臨床単離物とマウス感染モデルに対する化合物の活性を評価した.
主要な成果:
- リボシールCをE. coli*で高濃度に蓄積する化合物に成功させた.
- 野生型グラム陰性病原体に対する改変されたリボシルCの全細胞活性が実証された.
- グラム陰性感染症のマウスモデルでの有効性が確認された.
結論:
- リボシールCは 多剤耐性グラム陰性感染症に対する 新種の治療薬として有望です
- この研究は,グラム陰性細菌を標的とした抗生物質を開発するために予測ガイドラインを使用する戦略を検証しています.
- 改造されたリボシールCは,グラム陰性感染症の治療におけるFMNリボスイッチ結合剤のさらなる調査のためのプラットフォームを提供します.
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