Role of the VraDE transporter in differential susceptibility of S. aureus towards guanidine-containing lipopeptides and other cell wall targeting antibiotics (A09)

环状脂肽恩培多肽和三丙肽在结构上有相当大的相似性，但在效力和与细胞壁脂中间体的结合方式上有所不同。在这个项目中，我们研究了VraDE转运蛋白在金黄色葡萄球菌对这些环状脂肽和其他针对抗生素的细胞壁的不同敏感性中所起的细胞作用。具体地说，使用结构、生化和全细胞分析的组合，我们想要确定VraDE底物和肽聚糖生物合成网络中酶之间的相互作用伙伴。因此，我们的工作将揭开VraDE活性和细胞壁新陈代谢之间的联系，以及这如何导致对不同抗生素的耐药性。

The cyclic lipopeptides empedopeptin and tripropeptin share considerable structural similarity, yet differ in potency and their binding mode to cell wall lipid intermediates. In this project we investigate the cellular role of the VraDE transporter in the differential susceptibility of S. aureus towards these cyclic lipopeptides and other cell wall targeting antibiotics. Specifically, using a combination of structural, biochemical and whole cell analyses we want to identify VraDE substrates and interaction partners among enzymes from the peptidoglycan biosynthesis network. Thereby, our work will unravel the link between VraDE activity and cell wall metabolism and how this contributes to resistance to distinct antibiotics.