Bacillomycin D and mycosubtilin, antimicrobial lipopeptides from Bacillus subtilis. A comparative analysis of their interfacial properties

Bacillus subtilis strains produce antimicrobial lipopeptides using non ribosomal peptide synthesis pathway. Among them, those belonging to iturinic family have an important place. This family is characterized by a peptide ring with a constant LDDLLDL chiral amino acid sequence cycled by a -fatty acid with a variable acyl chain. The iturinic lipopeptides exhibit their biological activities on the plasma membrane of the microbial cells. It has been demonstrated that they could be active on pathogenic strains which are resistant to currently-used therapeutic agents. Despite their interesting antimicrobial properties, there is limited number of works on their interactions with plasma membranes in order to understand their mode of action. Langmuir monolayers at the air-water interface are a useful tool to analyze the interactions between antimicrobial lipopetides and membranes. We therefore investigated iturinic lipopeptides-membrane interactions using Langmuir monolayers as membrane model. Our work focused on two iturinics, mycosubtilin and bacillomycin D, differing by their peptide ring (Figure 1). In the first step, we investigated their interfacial properties using tensiometry measurements and polarization modulation infrared reflexion absorption spectroscopy (PM-IRRAS). We found that the ability to form an interfacial film for two lipopeptides was different depending on the nature of the subphase. Moreover, their conformations at the air-water interface were determined as turns. In the second step, we investigated the insertion of the mycosubtilin and bacillomycin D in the lipid monolayers by determining their exclusion surface pressures. Our results showed that the insertion depends on the nature of the lipid film hence a membrane-compostion-dependant action of the two antimicrobial compounds could be explained.