Staphylococcus aureus is a major bacterial pathogen that invades and damages host tissue by the expression of devastating toxins. We here performed a phenotypic screen of 35 molecules that were structurally inspired by previous hydroxyamide-based S. aureus virulence inhibitors compiled from commercial sources or designed and synthesized de novo. One of the most potent compounds, AV73, not only reduced hemolytic alpha-hemolysin production in S. aureus but also impeded in vitro biofilm formation. The effect of AV73 on bacterial proteomes and extracellular protein levels was analyzed by quantitative proteomics and revealed a significant down-regulation of major virulence and biofilm promoting proteins. To elucidate the mode of action of AV73, target identification was performed using affinity-based protein profiling (AfBPP), where among others YidC was identified as a target.

中文翻译：

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金黄色葡萄球菌毒力和生物膜的双重抑制剂减弱主要毒素和黏附素的表达。

金黄色葡萄球菌是主要细菌病原体，其通过破坏性毒素的表达侵入并破坏宿主组织。我们在这里进行了35个分子的表型筛选，这些分子在结构上受到以前的羟酰胺基金黄色葡萄球菌毒力抑制剂的启发，这些抑制剂是从商业渠道汇编或从头设计并合成的。最有效的化合物之一，AV73，不仅减少了金黄色葡萄球菌的溶血性α-溶血素的产生，而且还阻碍了体外生物膜的形成。AV73的效果通过定量蛋白质组学分析细菌蛋白质组和细胞外蛋白水平，发现主要毒力和生物膜促进蛋白显着下调。为了阐明AV73的作用方式，使用基于亲和力的蛋白质谱（AfBPP）进行靶标鉴定，其中，YidC被鉴定为靶标。