Antibiotic resistance is a growing global challenge to public health. Polymyxin is considered to be the last-resort antibiotic against most gram-negative bacteria. Recently, discoveries of a plasmid-mediated, transferable mobilized polymyxin resistance gene (mcr-1) in many countries have heralded the increased threat of the imminent emergence of pan-drug-resistant super bacteria. MCR-1 is an inner membrane protein that enables bacteria to develop resistance to polymyxin by transferring phosphoethanolamine to lipid A. However, the mechanism associated with polymyxin resistance has yet to be elucidated, and few drugs exist to address this issue. Here, we review our current understanding regarding MCR-1 and small molecule inhibitors to provide a detailed enzymatic mechanism of MCR-1 and the associated implications for drug design.

中文翻译：

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阐明质粒介导的大肠粘菌素抗性的分子机制和药物设计的最新进展。

抗生素耐药性是对公共卫生日益严峻的全球挑战。多粘菌素被认为是对抗大多数革兰氏阴性细菌的最后手段。最近，发现了质粒介导的，可转移的动员多粘菌素抗性基因（mcr-1）在许多国家已经预示着即将出现泛耐药性超级细菌的威胁越来越大。MCR-1是一种内膜蛋白，能够使细菌通过将磷酸乙醇胺转移到脂质A上来发展对多粘菌素的抗性。但是，与多粘菌素抗性相关的机制尚未阐明，目前很少有药物可以解决这个问题。在这里，我们回顾了有关MCR-1和小分子抑制剂的当前理解，以提供MCR-1的详细酶促机理及其对药物设计的影响。