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

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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.