On the antibacterial action of aurein 1.2 and maculatin 1.1 peptides over complex bilayers with differential glycolipid content. A multidisciplinary study using coarse-grained molecular dynamics simulations.

AYELEN A HUGO; PÉREZ PF2; PICKHOLZ M.; SZYMANOWSKI F; GÓMEZ-ZAVAGLIA A2; MARTINI M. F.; BALATTI GE; AMBROGGIO EE3; FIDELIO GD

La Plata

Simposio; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

The antimicrobial peptides (AMPs) are key molecules of the innate immune system that exert their action mainly against bacteria. It was suggested in the literature that AMPs act by increasing the permeability of the membrane after an initial peptide-lipid interaction. Among AMPs, the peptids aurein 1.2 and maculatin 1.1 exhibit a well-proven lytic activity and, previously, we shed light about the molecular mechanism by which they damage different biomembranes by combined computational and experimental approaches. We also found that the Lactobacillus delbrueckii subsp. lactis (CIDCA133) and the L. delbrueckii subsp. bulgaricus (CIDCA331) strains of lactic bacteria show differential susceptibility to the antimicrobial action of several AMPs, including aurein and maculatin.Considering that membrane composition is a key aspect of the early peptide-lipid interaction and that the resistant strain shows significant amounts of glycolipids, we defined a set of different model membranes and carried out extensive Molecular Dynamics (MD) within the MARTINI coarse-grain force field. Since both peptides are archetypical helicoidal AMPs but they seem to act by different molecular mechanisms, the aim was to understand how the lipid composition is related with the resistance to the action of that kind of peptides.The results show a capability of both peptides to affect membrane bilayers, but the different membranes are differentially affected. In effect, we found a strong correlation between the proportion of glycolipids in the membrane mix and the ability to keep the membrane integrity against the peptides antimicrobial action. In addition, and as we pointed in previous works, maculatin can induce membrane local curvature in the mixes, despite the glycolipid presence. Each model membrane shows differential molecular behavior with the AMP molecules, and the use of coarse-grained simulations supported by experimental techniques can help to elucidate the specific molecular factors that allow certain lipid bilayer configurations to resist or diminish the effects of AMPs against them.