Biomimetic approaches to understand how mycosubtilin, an antifungal lipopeptide, can interact with cytoplasmic membranes

Mycosubtilin is a natural cyclic lipopeptide characterized by its strong antifungal activities. It has been demonstrated that the cytoplasmic membranes of the sensitive cells are the target of this antifungal lipopeptide. In spite of the fact that some properties of mycosubtilin have been highlighted, the molecular mechanism of its biological action remains partially understood. In view of this, we investigated the interactions between mycosubtilin and cytoplasmic membranes by using biomimetic systems such as lipid monolayers at the air-water interface and lipid multilayers. These interactions were examined by different methods (pressure/area isotherms, kinetic measurements of the interfacial adsorption, Brewster angle microscopy, infrared and NMR spectroscopies). We showed that mycosubtilin does not interact strongly with the C=O ester residues of phospholipids in multilayers, while it modifies the transition temperature of the alkyl chains. It was also demonstrated that these interactions depend on the phospholipid phase. Varying the lipid composition of monolayers allowed us to demonstrate an original behavior of mycosubtilin in the presence of sterol. This suggests a mycosubtilin-sterol affinity.