Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically relevant bacteria is the horizontal transfer of ABR genes mediated by plasmids. Here, we report the first analysis of CS associated with the acquisition of complete ABR plasmids, including the clinically important carbapenem-resistance conjugative plasmid pOXA-48. In addition, we describe the conservation of CS in clinical E. coli isolates and its application to selectively kill plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR.

中文翻译：

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与抗生素抗性质粒相关的附带敏感性

附带敏感性 (CS) 是一种很有前途的替代方法，可以应对日益严重的抗生素耐药性 (ABR) 问题。当对一种抗生素产生耐药性导致对第二种抗生素的敏感性增加时，就会发生 CS。最近的研究集中在针对由染色体突变介导的 ABR 设计的 CS 策略。然而，临床相关细菌中 ABR 的主要驱动因素之一是由质粒介导的 ABR 基因的水平转移。在这里，我们报告了与获得完整 ABR 质粒相关的 CS 的首次分析，包括临床上重要的碳青霉烯类抗性结合质粒 pOXA-48。此外，我们描述了 CS 在临床大肠杆菌分离物中的保护作用及其在选择性杀死携带质粒的细菌中的应用。