Characterization of mycosubtilin, a natural antifungal agent, in membrane biomimetic systems

The emergence of several diseases which affects immune system (HIV infections, few cancers) and the expansion of immunosuppressive and chemical anticancer therapies increase mycosis frequency. Treatments currently used to cure mycoses meet problems such as antifungal agent toxicity or pathogenic strain resistance. Thus there is increasing interest for new medical applications of antifungal molecules. In this context, we investigated the behaviour of an antifungal lipopeptide, mycosubtilin, on cytoplasmic membranes. In this aim, biomimetic systems of biological membranes, such as lipid monolayers at the air-water interface and lipid multilayers were used. The interactions of mycosubtilin with these biomimetic systems were examined by different methods (kinetic isotherms, Brewster angle microscopy, FTIR spectroscopy and 1H HR- Magic Angle Spinning NMR). We demonstrated an original behaviour of mycosubtilin in the presence of sterol monolayer, suggesting a mycosubtilin-sterol affinity. We showed as well that mycosubtilin can interact with C=O ester residues and alkyl chains of phospholipids. Moreover, mycosubtilin has a preference for condensed phospholipid domains.