Investigating the Impact of the Glycolipid Content on Aurein 1.2 Pores in Prokaryotic Model Bilayers: A Coarse-Grain Molecular Dynamics Simulation Study

• DOI: 10.1021/acs.jpcb.3c01053
• Publication Date: 2023-05-31T15:17:00Z
• Authors: G. E. Balatti; M. F. Martini; M. Pickholz
• Keywords: ANTIMICROBIAL RESISTANCE; https://purl.org/becyt/ford/1.6; https://purl.org/becyt/ford/3.1; Lipid Bilayers; Cell Membrane; MOLECULAR DYNAMICS; https://purl.org/becyt/ford/3; Molecular Dynamics Simulation; Glycolipids; ANTIMICROBIAL PEPTIDES; https://purl.org/becyt/ford/1; Antimicrobial Cationic Peptides

Aurein 1.2 is an antimicrobial peptide (AMP) with known lytic activity against bacterial membranes. Our previous studies revealed a differential action of aurein by both experimental and computational methods. This differential action was over membranes of two related probiotic strains, where the main difference between membranes was the number of glycolipids in the lipid composition. In this work, we aimed to investigate the interaction of aurein 1.2 with model bacterial membranes of varying glycolipid content. To this end, we performed extensive molecular dynamics simulations using the MARTINI coarse-grain force field and differential mixtures of phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and monogalactosylglycerol (MG). We found a correlation between the presence of MG in PG/PE mixtures and the difficulty of aurein to stabilize pore structures, suggesting an AMP-resistance factor encoded in the lipid composition of the membrane. These findings may shed light on a possible mechanism of bacterial resistance to AMPs that is related to the glycolipid content of bacterial membranes.