Regulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.
Regulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.
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DOI：
10.1016/j.chembiol.2016.01.004
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发表时间：
2016-02-18
影响因子：
8.6
通讯作者：
Muir TW
中科院分区：
文献类型：
--
作者：
Wang B;Muir TW
agr 基因座编码一系列革兰氏阳性病原体的毒力所需的群体感应（QS）电路，因此被视为化疗药物开发的重要靶点。近年来，金黄色葡萄球菌 agr 回路中的许多生化事件已被重建并进行体外定量分析。这项工作与信号通路中几个关键参与者的结构研究相结合，为 agr 群体感应系统的调节和进化提供了机制上的见解。在此，我们回顾这一进展并讨论该领域剩余的悬而未决的问题。我们还重点介绍了小分子 agr 调节剂的发现进展，以及如何利用新获得的生化和结构信息来设计针对 agr 系统的下一代疗法。
The agr locus encodes a quorum sensing (QS) circuit required for the virulence of a spectrum of gram-positive pathogens and is, therefore, regarded as an important target for the development of chemotherapeutics. In recent years, many of the biochemical events in the Staphylococcus aureus agr circuit have been reconstituted and subject to quantitative analysis in vitro. This work, in conjunction with structural studies on several key players in the signaling circuit, has furnished mechanistic insights into the regulation and evolution of the agr quorum sensing system. Herein, we review this progress and discuss the remaining open questions in the area. We also highlight advances in the discovery of small-molecule agr modulators and how the newly available biochemical and structural information might be leveraged for the design of next generation therapeutics targeting the agr system.