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大规模实验室进化揭示了临床相关的附带抗生素敏感性

Farhan R Chowdhury¹, Veronica Banari², Vlada Lesnic²

¹Department of Biology, Concordia University, Montréal, Québec, Canada.

International journal of antimicrobial agents

|July 4, 2025

概括

附带敏感性 (CS) 疗法可以对抗抗生素耐药性. 在大肠杆菌中,tigecycline和polymyxin B之间的新型CS链接在实验室进化方法中强大,并在临床分离物中发现,为抗药性提供了新的策略.

科学领域:

微生物学微生物学
进化生物学进化生物学
药理学药理学是指药理学的学科.

背景情况:

抗生素耐药性是一个日益增长的全球健康威胁.
附带敏感性 (CS) 序列疗法是缓解耐药性演变的有希望的策略.
CS相互作用的重复性和临床相关性需要进一步研究.

研究的目的:

在不同的实验室适应性进化 (ALE) 条件下评估CS相互作用的进化重复性.
为了确定新的CS关系与潜在的临床应用.
确定不同ALE平台对临床CS效应的预测能力.

主要方法:

使用三种不同的ALE平台,对抗tigecycline (TIG) 和piperacillin (PIP) 的大肠杆菌多个系谱的演化.
产生了超过130个耐药突变,并进行了540个耐药性和CS测量.
分析了超过750个多药耐药 (MDR) 大肠杆菌分离物的临床数据集.

主要成果:

在所有ALE平台上确定了TIG和polymyxin B (POL) 之间的高度可重复的CS关系.
该机制涉及TIG耐药性,导致Lon蛋白酶失活和外聚糖过度产生,导致对POL的过敏.
软基梯度演变 (SAGE) 平台展示了对临床附带效应的最佳预测.

结论:

发现的TIG-POL CS相互作用是强大的,并在不同的进化微环境中得到保护.
这种CS关系存在于临床泌尿病原体MDR大肠杆菌分离物中.
建立了一个用于识别临床相关和强大的CS相互作用的框架,有助于制定打击抗生素耐药性的战略.

关键词:

适应性实验室进化的演变.抗生素耐药性抗生素耐药性担保的敏感性担保的敏感性

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