Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing.

Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing.
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DOI:
10.1093/femsre/fuy031
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发表时间:
2018-11-01
影响因子:
11.3
通讯作者:
Piddock LJV
Piddock LJV
中科院分区:
生物学1区
文献类型:
--
作者:
Buckner MMC;Ciusa ML;Piddock LJV

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抗菌素耐药性(AMR)是一个阻碍细菌感染治疗的全球性问题,使现代医学的许多方面变得不那么有效。AMR基因(ARGs)通常位于质粒上,质粒是DNA的自我复制元素。它们通常在细菌之间传播,有些已经在全球传播。抗击抗生素耐药性需要新的策略,质粒固化和抗质粒方法可以减少ARG的流行,并使细菌对抗生素敏感。我们讨论了固化剂作为实验室工具的使用,包括化学品(如洗涤剂和插层剂),医学中使用的药物,包括抗坏血酸,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。新的策略进行了审查;其中包括偶联抑制剂(如TraE抑制剂、亚油酸、油酸、2-十六酸和坦桑酸)、围绕质粒不相容设计的系统、噬菌体和基于CRISPR/ cas的方法。目前,普遍缺乏体内治疗的选择。本综述强调了这一重要缺陷,如果能够填补这一缺陷,将为减少人类和动物中ARG的流行提供一种有希望的机制。由于环境中存在高水平的ARGs,因此不适合在体内使用的质粒固化机制对于减轻全球抗菌素耐药性负担仍然很重要。从不同生态系统中的细菌中去除质粒可能是对抗抗菌素耐药性的一个重要方面。
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. Removing plasmids from bacteria in different ecosystems could be an important aspect of fighting antimicrobial resistance.
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