title: Interactions of the natural antimicrobial mycosubtilin with phospholipid membrane models.
abstract: Among the secondary metabolite lipopeptides produced by Bacillus subtilis, mycosubtilin is characterized by its strong antifungal activities. Even though its structure and its cellular target, the cytoplasmic membrane, have been determined, the molecular mechanisms of the biological activity of mycosubtilin have not been completely elucidated. In this work, the interactions between mycosubtilin and cytoplasmic membranes were modelled by using biomimetic systems such as Langmuir monolayers at the air-water interface and lipid multilamellar vesicles. The interactions of mycosubtilin with these biomimetic systems were examined, for the first time, by using specific techniques such as polarization modulation infrared reflection absorption spectroscopy, Brewster angle microscopy and high-resolution magic angle spinning NMR. Our findings indicate that mycosubtilin alone, at the air-water interface, forms a monolayer film and keeps its turn conformation. In the presence of DMPC, mycosubtilin binds to phospholipid monolayers, in a surface pressure-dependent manner. This binding results in the appearance of condensed domains which can be due to the formation of mycosubtilin clusters and/or to the lipopeptide aggregation with some phospholipid molecules and/or the formation of liquid-condensed domains of DMPC. Furthermore, in multilamellar vesicles, the mycosubtilin-DMPC interactions take place at the level of the aliphatic chains of the phospholipid because the phase transition temperature of DMPC decreased in the presence of mycosubtilin.
authors.affiliation: Université de Lyon, Villeurbanne, France.
authors.forename: Mehmet N
authors.initials: MN
authors.lastname: Nasir
authors.forename: Ankita
authors.initials: A
authors.lastname: Thawani
authors.forename: Achraf
authors.initials: A
authors.lastname: Kouzayha
authors.forename: Françoise
authors.initials: F
authors.lastname: Besson
mesh_terms: D000388:Air; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008954:Models, Biological; D008968:Molecular Conformation; D010743:Phospholipids / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014867:Water
chemical_list: D000900:Anti-Bacterial Agents; D008074:Lipoproteins; D008567:Membranes, Artificial; D010743:Phospholipids; D014867:Water; C012448:mycosubtiline; D004134:Dimyristoylphosphatidylcholine