抗菌药物的耐药性对于全球公共健康的威胁日益增长。在ESKAPE生物体中的多药耐药性是需要特别关注的，ESKAPE生物体包括屎肠球菌，金黄色葡萄球菌，肺炎杆菌，鲍曼不动杆菌，铜绿假单胞菌和肠杆菌属，在医院中这些细菌经常导致许多严重感染。尽管目前已经有一些很有前景的药物处于临床试验中，但仍然迫切需要新的抗生素结构。研究人员抗菌一直在努力找出新的具有有效细胞活性的小分子药物，尤其是一些能够有效对抗多药耐药革兰阴性菌的小分子药物。但是开发出新药仍然十分困难，这种困难的根源在于目前对化合物透过细菌膜的外排系统的研究并不十分清楚。发表于《自然评论:药物发现》(Nature reviews. Drug discovery)2015年6月的一篇评论文章，将阿斯利康过去十年中的以靶点为基础的表型筛选方面的结果进行了总结，讨论了一些后续的化学结构方面的挑战，总结了新的办法，包括计算模型和先进的生物工具，为发现新的抗菌剂铺平道路。

        原文摘要：

        ESKAPEing the labyrinth of antibacterial discovery.

        Tommasi R1, Brown DG2, Walkup GK3, Manchester JI4, Miller AA1.

        Author information

        Abstract

        Antimicrobial drug resistance is a growing threat to global public health. Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - is of particular concern because they are responsible for many serious infections in hospitals. Although some promising agents are in the pipeline, there is an urgent need for new antibiotic scaffolds. However, antibacterial researchers have struggled to identify new small molecules with meaningful cellular activity, especially those effective against multidrug-resistant Gram-negative pathogens. This difficulty ultimately stems from an incomplete understanding of efflux systems and compound permeation through bacterial membranes. This Opinion article describes findings from target-based and phenotypic screening efforts carried out at AstraZeneca over the past decade, discusses some of the subsequent chemistry challenges and concludes with a description of new approaches comprising a combination of computational modelling and advanced biological tools which may pave the way towards thediscovery of new antibacterial agents.