Structural biology of MCR-1-mediated resistance to polymyxin antibiotics.
Structural biology of MCR-1-mediated resistance to polymyxin antibiotics.
复制标题
MCR-1介导的多粘菌素抗生素耐药性的结构生物学。
DOI：
10.1016/j.sbi.2023.102647
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发表时间：
2023-07
影响因子：
6.8
通讯作者：
I. C. Materon;T. Palzkill
中科院分区：
文献类型：
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作者：
I. C. Materon;T. Palzkill
多粘菌素是一种最后的抗生素，针对病原体的外膜，用于解决日益普遍的多重耐药革兰氏阴性细菌。质粒编码酶MCR-1通过修饰外膜赋予细菌多粘菌素抗性。对多粘菌素的可转移性耐药性是一个主要问题；因此，MCR-1是一个重要的药物靶点。在这篇综述中，我们讨论了最近的结构和机制方面的MCR-1功能，它的变体和同源物，以及它们如何与多粘菌素耐药性相关。具体来说，我们讨论了多粘菌素介导的内外膜破坏，MCR-1催化机制的计算研究，对MCR-1中底物结合重要残基的诱变和结构分析，以及针对MCR-1的抑制剂的进展。
Polymyxins, a last resort antibiotic, target the outer membrane of pathogens and are used to address the increasing prevalence of multidrug-resistant Gram-negative bacteria. The plasmid-encoded enzyme MCR-1 confers polymyxin resistance to bacteria by modifying the outer membrane. Transferable resistance to polymyxins is a major concern; therefore, MCR-1 is an important drug target. In this review, we discuss recent structural and mechanistic aspects of MCR-1 function, its variants and homologs, and how they are relevant to polymyxin resistance. Specifically, we discuss work on polymyxin-mediated disruption of the outer and inner membranes, computational studies on the catalytic mechanism of MCR-1, mutagenesis and structural analysis concerning residues important for substrate binding in MCR-1, and finally, advancements in inhibitors targeting MCR-1.