PDF(Pubmed)
Abstract：
Gram-negative bacteria are uniquely equipped to defeat antibiotics. Their outermost layer, the cell envelope, is a natural permeability barrier that contains an array of resistance proteins capable of neutralizing most existing antimicrobials. As a result, its presence creates a major obstacle for the treatment of resistant infections and for the development of new antibiotics. Despite this seemingly impenetrable armor, in-depth understanding of the cell envelope, including structural, functional and systems biology insights, has promoted efforts to target it that can ultimately lead to the generation of new antibacterial therapies. In this article, we broadly overview the biology of the cell envelope and highlight attempts and successes in generating inhibitors that impair its function or biogenesis. We argue that the very structure that has hampered antibiotic discovery for decades has untapped potential for the design of novel next-generation therapeutics against bacterial pathogens.
摘要：
革兰氏阴性菌具有击败抗生素的独特能力。它们的最外层，细胞包膜，是一种天然的渗透屏障，包含一系列能够中和大多数现有抗菌剂的抗性蛋白。因此,它的存在为耐药感染的治疗和新抗生素的开发创造了一个主要障碍。尽管这似乎无法穿透的盔甲，深入了解细胞包膜，包括结构性的,功能和系统生物学见解，促进了针对它的努力，最终可以导致新的抗菌疗法的产生。在这篇文章中,我们对细胞包膜的生物学进行了广泛的概述，并重点介绍了在产生损害其功能或生物发生的抑制剂方面的尝试和成功。我们认为，几十年来阻碍抗生素发现的结构尚未开发出针对细菌病原体的新型下一代疗法的设计潜力。
