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对agr群体感应系统的化学和生物分子见解:当前进展与持续挑战

Chemical and biomolecular insights into the agr quorum sensing system: Current progress and ongoing challenges.

作者信息

Polaske Thomas J, West Korbin H J, Zhao Ke, Widner Danielle L, York Jordan T, Blackwell Helen E

机构信息

Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706 USA.

出版信息

Isr J Chem. 2023 Jun;63(5-6). doi: 10.1002/ijch.202200096. Epub 2023 Mar 16.

Abstract

is a ubiquitous bacterium that has become a major threat to human health due to its extensive toxin production and tremendous capacity for antibiotic resistance (e.g., MRSA "superbug" infections). Amid a worsening antibiotic resistance crisis, new strategies to combat this deadly microbe that remove the selective pressure of traditional approaches are in high demand. utilizes an accessory gene regulator () quorum sensing network to monitor its local cellular population and trigger a devastating communal attack, like an invading horde, once a threshold cell density has been reached. The role of the system in a range of disease types is still being unraveled. Herein, we discuss the present-day biochemical understanding of along with unresolved details, describe its connection to the progression of infection, and review how chemical strategies have been implemented to study and intercept this signaling pathway. This research is illuminating the potential of as an anti-virulence target in and should inform the study of similar, yet less studied, systems in related bacterial pathogens.

摘要

是一种普遍存在的细菌,由于其大量产生毒素以及具有极强的抗生素耐药能力(例如耐甲氧西林金黄色葡萄球菌“超级细菌”感染),已成为对人类健康的重大威胁。在日益严重的抗生素耐药危机中,对抗这种致命微生物的新策略需求迫切,这些新策略需消除传统方法的选择压力。利用一种辅助基因调控()群体感应网络来监测其局部细胞群体,并在达到阈值细胞密度时触发一场毁灭性的群体攻击,就像入侵的部落一样。系统在一系列疾病类型中的作用仍在被逐步揭示。在此,我们讨论目前对的生化理解以及尚未解决的细节,描述其与感染进展的联系,并回顾如何实施化学策略来研究和阻断这条信号通路。这项研究揭示了作为中的抗毒力靶点的潜力,并且应为相关细菌病原体中类似但研究较少的系统的研究提供参考。

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