Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, USA.
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Dr., Madison, WI 53706, USA.
Cell Chem Biol. 2022 Apr 21;29(4):605-614.e4. doi: 10.1016/j.chembiol.2021.12.005. Epub 2021 Dec 20.
Strategies to both monitor and block bacterial quorum sensing (QS), and thus associated infections, are of significant interest. We developed a straightforward assay to monitor biosurfactants and lytic agents produced by bacteria under the control of QS. The method is based on the lysis of synthetic lipid vesicles containing the environmentally sensitive fluorescent dye calcein. This assay allows for the in situ screening of compounds capable of altering biosurfactant production by bacteria, and thereby the identification of molecules that could potentially modulate QS pathways, and avoids the constraints of many of the cell-based assays in use today. Application of this assay in a high-throughput format revealed five molecules capable of blocking vesicle lysis by S. aureus. Two of these compounds were found to almost completely inhibit agr-based QS in S. aureus and represent the most potent small-molecule-derived QS inhibitors reported in this formidable pathogen.
监测和阻断细菌群体感应（QS）以及相关感染的策略具有重要意义。我们开发了一种简单的测定方法，用于监测 QS 控制下细菌产生的生物表面活性剂和溶菌剂。该方法基于含有环境敏感荧光染料钙黄绿素的合成脂质体的裂解。该测定法可用于原位筛选能够改变细菌生物表面活性剂产生的化合物，从而鉴定可能调节 QS 途径的分子，并避免当今许多基于细胞的测定法的限制。该测定法在高通量格式中的应用揭示了五种能够阻止金黄色葡萄球菌裂解脂质体的分子。其中两种化合物被发现几乎完全抑制了金黄色葡萄球菌中的 agr 基 QS，代表了在这种强大病原体中报道的最有效的小分子衍生的 QS 抑制剂。
