摘要

       抗生素耐药性（AMR）是一个全球性的问题，阻碍了细菌感染的治疗，使现代医学的许多方面效果不佳。AMR基因（ARGs）常位于质粒上，是DNA的自我复制元件。它们经常在细菌之间传播，有些已经在全球传播。抗AMR需要新的策略，而质粒治疗和抗质粒治疗可以降低ARG的患病率，并使细菌对抗生素敏感。我们讨论使用固化剂作为实验室工具，包括化学品（如洗涤剂和插层剂）、药物（如抗坏血酸）、精神药物（如氯丙嗪）、抗生素（如氨基香豆素、喹诺酮类和利福平）和植物衍生化合物。研究了新的策略：包括结合抑制剂（如TraE抑制剂、亚油酸、油酸、2-十六烯酸和坦桑尼亚酸）、围绕质粒不相容性设计的系统、噬菌体和基于CRISPR/Cas的方法。目前，体内治疗方案普遍缺乏。这篇综述强调了这一重要缺陷，如果填补了这一缺陷，将为降低人类和动物体内精氨酸的流行提供一个有希望的机制。由于环境中存在高水平的ARGs，不适合在体内使用的质粒固化机制对于降低AMR的整体负担仍然是重要的。

      Antimicrobial resistance (AMR) is a global problem hindering treatment of bacterial infections, rendering many aspects of modern medicine less effective. AMR genes (ARGs) are frequently located on plasmids, which are self-replicating elements of DNA. They are often transmissible between bacteria, and some have spread globally. Novel strategies to combat AMR are needed, and plasmid curing and anti-plasmid approaches could reduce ARG prevalence, and sensitise bacteria to antibiotics. We discuss the use of curing agents as laboratory tools including chemicals (e.g. detergents and intercalating agents), drugs used in medicine including ascorbic acid, psychotropic drugs (e.g. chlorpromazine), antibiotics (e.g. aminocoumarins, quinolones and rifampicin) and plant-derived compounds. Novel strategies are examined; these include conjugation inhibitors (e.g. TraE inhibitors, linoleic, oleic, 2-hexadecynoic and tanzawaic acids), systems designed around plasmid incompatibility, phages and CRISPR/Cas-based approaches. Currently, there is a general lack of in vivo curing options. This review highlights this important shortfall, which if filled could provide a promising mechanism to reduce ARG prevalence in humans and animals. Plasmid curing mechanisms which are not suitable for in vivo use could still prove important for reducing the global burden of AMR, as high levels of ARGs exist in the environment.

       https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199537/