Towards anti-virulence drugs targeting ESX-1 mediated pathogenesis of Mycobacterium tuberculosis

Jeffrey M. Chen , Florence Pojer , Benjamin Blasco, Stewart T. Cole
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引用次数: 23

Abstract

The control of tuberculosis (TB) in humans is heavily reliant on short course chemotherapy yet this intervention is increasingly menaced by widespread multi- and extensively drug resistant strains of Mycobacterium tuberculosis. New druggable targets and novel leads are required for TB drug discovery to develop compounds with greater potency, and that are less prone to acquired drug resistance. As such, the concept of blocking the secretion of virulence proteins and modulating their effect with small molecules has gained increasing attention in recent years. Here, we propose targeting the principal virulence determinant of M. tuberculosis, the ESX-1 protein secretion system and its downstream effects, to discover new drugs and augment the dwindling armoury of effective antitubercular agents.

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针对ESX-1介导的结核分枝杆菌发病机制的抗毒药物研究
人类结核病的控制严重依赖于短期化疗,但这种干预日益受到广泛存在的多重和广泛耐药结核分枝杆菌菌株的威胁。结核病药物发现需要新的可药物靶点和新的线索,以开发具有更强效力的化合物,并且不易产生获得性耐药。因此,近年来,阻断毒力蛋白的分泌并通过小分子调节其作用的概念越来越受到关注。在这里,我们建议针对结核分枝杆菌的主要毒力决定因素,ESX-1蛋白分泌系统及其下游效应,发现新的药物并增加有效抗结核药物的减少。
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