Physicochemical Characterization of Daptomycin Interaction with Negatively Charged Lipid Membranes

Daptomycin is known as an effective antibiotic lipopeptide which shows activity against the number of Gram-positivepathogens. Its primary target is the bacterial cell membrane. However, the detailed mechanism of daptomycin action is still subject todebate. In this paper, we have investigated the interactions between lipopeptide and model lipidfilms composed of negativelycharged phosphatidylglycerols and cardiolipin. In order to evaluate the effect of daptomycin on the molecular organization and theproperties of lipid assemblies, we have used surface pressure measurements and electrochemical methods combined with atomicforce microscopy, quartz crystal microbalance, and surface-enhanced infrared absorption spectroscopy. Our results indicate thatdaptomycin interaction with the lipid membrane is complex. It involves daptomycin aggregation and partial insertion, which in turnaffect the charge distribution on both sides of the membrane and may result in a gradient of water chemical potential. The latter candrive theflux of water across the membrane.