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体外筛选群体感应抑制剂及体内确认其效果。

In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect.

机构信息

Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Nat Protoc. 2010 Feb;5(2):282-93. doi: 10.1038/nprot.2009.205. Epub 2010 Jan 28.

DOI:10.1038/nprot.2009.205
PMID:20134428
Abstract

This article will introduce the reader to protocols intended for (i) identification of quorum sensing (QS) inhibitors (QSIs), (ii) characterization of these compounds in vitro and (iii) evaluation of these compounds in animal models. Traditional antimicrobial drugs are designed against planktonic bacteria and not against bacterial biofilms. In biofilms, bacteria are highly resistant to otherwise lethal treatments and they communicate with each other, thus enabling coordinated group behavior. For many years, we have focused on interference with cell to cell communication, also known as QS, with the aim of disabling the expression of virulence and reduction of antibiotic tolerance. Here we present protocols for screening and testing for acyl-homoserine lactone (AHL)-dependent QS inhibition. We also present protocols for the in vivo validation of QSIs as possible drug candidates. The presented methods allow the evaluation of QS inhibition by a potential drug candidate within 2-3 weeks.

摘要

本文将向读者介绍旨在(i)鉴定群体感应(QS)抑制剂(QSIs),(ii)在体外对这些化合物进行表征和(iii)在动物模型中评估这些化合物的方案。传统的抗菌药物是针对浮游细菌而不是针对细菌生物膜设计的。在生物膜中,细菌对其他致死性治疗具有高度抗性,并且它们相互通信,从而实现协调的群体行为。多年来,我们一直专注于干扰细胞间通讯,也称为 QS,目的是使毒力表达失活和降低抗生素耐药性。在这里,我们介绍了用于筛选和测试酰基高丝氨酸内酯(AHL)依赖性 QS 抑制的方案。我们还介绍了用于体内验证 QSIs 作为潜在药物候选物的方案。所提出的方法允许在 2-3 周内评估潜在药物候选物的 QS 抑制作用。

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