Effect of lipid composition and peptide sequence on the interaction between myxinidin and model membranes

Antimicrobial peptides (AMPs) are a promising class of compounds that could resolve the problem of antibiotic resistance caused by pathogenic bacteria. They constitute an essential component of the innate immune response, and have been isolated from a broad range of organisms [1]. Myxinidin, a novel AMP derived from the epidermal mucus of hagfish Myxine glutinosa L., has shown potent antimicrobial activity against a wide range of Gram-negative and Gram-positive bacteria [2]. In this study, we report calorimetric and spectroscopic results on the interaction between myxinidin and its mutant (WMR) with liposomes as model bio-membranes. We tested liposomes of different lipid composition, DOPE/ DOPG (80/20) and DOPE/DOPG/CL (65/23/12), mimicking E. coli and P. aeruginosa membranes. Our results pointed out that, besides the peptide sequence, the membrane lipid composition plays a pivotal role in the peptide-membrane interaction. The mutant WMR, which contains a tryptophan residue at its N-terminus and a higher number of positively charged amino acid (arginine) residues compared to myxinidin, has a preferential interaction with liposomes containing the anionic lipid CL. In addition, WMR is capable to induce the segregation of anionic CL and possibly favours membrane pore formation. On the contrary, myxinidin causes a significant perturbing effect on the lipid acyl chains of the liposomes without CL; it barely interacts with both membranes and does not induce rearrangements of the lipids into domains. These results confirm the importance of both peptide sequences and lipid compositions on the mechanism of membrane perturbation caused by antimicrobial peptides.