Methods to assay inhibitors of DNA gyrase and topoisomerase IV activities.

L Mark Fisher, Xiao-Su Pan
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引用次数: 40

Abstract

DNA gyrase and DNA topoisomerase (topo) IV are the bacterial targets of coumarin and quinolone antimicrobial agents. Widespread resistance to clinically important antibiotics such as beta-lactams and macrolides has stimulated the development of novel gyrase and topo IV inhibitors especially against Streptococcus pneumoniae and other Gram-positive pathogens. Here, we describe how gyrase and topo IV activities are measured and how inhibitors of these enzymes may be assayed, focusing as a paradigm on DNA supercoiling by S. pneumoniae gyrase, DNA decatenation by S. pneumoniae topo IV, and DNA cleavage by both enzymes. These approaches provide mechanistic insight on inhibitor action and allow identification of dual gyrase/topo IV targeting agents that can minimize the emergence of bacterial resistance.

方法测定DNA旋切酶和拓扑异构酶抑制剂的活性。
DNA回转酶和DNA拓扑异构酶(topo) IV是香豆素和喹诺酮类抗菌药物的细菌靶点。对临床上重要抗生素(如β -内酰胺类和大环内酯类)的广泛耐药性刺激了新型gyrase和topo IV抑制剂的发展,特别是针对肺炎链球菌和其他革兰氏阳性病原体。在这里,我们描述了如何测量旋转酶和topo IV的活性,以及如何检测这些酶的抑制剂,重点关注肺炎链球菌旋转酶的DNA超缠绕,肺炎链球菌topo IV的DNA十烷化,以及这两种酶的DNA切割。这些方法提供了抑制剂作用的机理,并允许识别双重gyrase/topo IV靶向剂,可以最大限度地减少细菌耐药性的出现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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