Department of Pathogen Biology and Microbiology, and Department of General Intensive Care Unit of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Pathogen Biology and Microbiology, and Department of General Intensive Care Unit of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Trends Biochem Sci. 2019 Nov;44(11):973-988. doi: 10.1016/j.tibs.2019.06.002. Epub 2019 Jul 3.
Polymyxins are a group of detergent-like antimicrobial peptides that are the ultimate line of defense against carbapenem-resistant pathogens in clinical settings. Polymyxin resistance primarily originates from structural remodeling of lipid A anchored on bacterial surfaces. We integrate genetic, structural, and biochemical aspects of three major types of lipid A modifiers that have been shown to confer intrinsic colistin resistance. Namely, we highlight ArnT, a glycosyltransferase, EptA, a phosphoethanolamine transferase, and the AlmEFG tripartite system, which is restricted to EI Tor biotype of Vibrio cholerae O1. We also discuss the growing family of mobile colistin resistance (MCR) enzymes, each of which is analogous to EptA, and which pose great challenges to global public health.
多黏菌素是一组去污剂样的抗菌肽，是临床应对碳青霉烯类耐药病原体的最后一道防线。多黏菌素耐药主要源于细菌表面锚定的脂质 A 的结构重塑。我们整合了三种主要类型的脂质 A 修饰物的遗传、结构和生化方面的信息，这些修饰物已被证明可赋予固有粘菌素耐药性。即，我们重点介绍 ArnT，一种糖基转移酶、EptA，一种磷酸乙醇胺转移酶和仅限于霍乱弧菌 O1 EI Tor 生物型的 AlmEFG 三联体系统。我们还讨论了日益增多的可移动粘菌素耐药（MCR）酶家族，它们每一个都类似于 EptA，对全球公共健康构成了巨大挑战。
