抗菌藥物的耐藥性對於全球公共健康的威脅日益增長。在ESKAPE生物體中的多藥耐藥性是需要特別關注的，ESKAPE生物體包括屎腸球菌，金黃色葡萄球菌，肺炎杆菌，鮑曼不動杆菌，銅綠假單胞菌和腸杆菌屬，在醫院中這些細菌經常導致許多嚴重感染。盡管目前已經有一些很有前景的藥物處於臨床試驗中，但仍然迫切需要新的抗生素結構。研究人員抗菌一直在努力找出新的具有有效細胞活性的小分子藥物，尤其是一些能夠有效對抗多藥耐藥革蘭陰性菌的小分子藥物。但是開發出新藥仍然十分困難，這種困難的根源在於目前對化合物透過細菌膜的外排係統的研究並不十分清楚。發表於《自然評論:藥物發現》(Nature reviews. Drug discovery)2015年6月的一篇評論文章，將阿斯利康過去十年中的以靶點為基礎的表型篩選方麵的結果進行了總結，討論了一些後續的化學結構方麵的挑戰，總結了新的辦法，包括計算模型和先進的生物工具，為發現新的抗菌劑鋪平道路。

原文摘要：

ESKAPEing the labyrinth of antibacterial discovery.

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

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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.