On the antibacterial action of aurein 1.2 and maculatin 1.1 peptides over complex bilayers with differential glycolipid content. A multidisciplinary study using computational and experimental methods

BALATTI, GALO EZEQUIEL

La Plata

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

Sociedad Argentina de Biofísica

The antimicrobial peptides (AMPs) are key molecules of the innate immune system that exert their action mainly against bacteria. It was suggested that AMPs act by increasing the permeability of the membrane after an initial peptide-lipid interaction. Among AMPs, the aurein and the maculatin 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 action of several AMPs, including aurein and maculatin.Considering that bilayer composition is a key aspect of the early peptide-lipid interaction and that the resistant strain shows high amounts of glycolipids, we defined a set of different model membranes and carried out extensive Molecular Dynamics (MD) within the MARTINI coarse-grain (CG) force field. Since both peptides are 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 and the ability to keep the membrane integrity against the AMP action. In addition, and as we pointed in previous works, maculatin can induce membrane curvature in the bilayers, despite the glycolipid presence. Each model membrane shows differential molecular behavior with the AMP molecules, and the use of CG simulations supported by experimental techniques can help to elucidate the specific molecular factors that allow certain bilayer configurations to resist or diminish the effects ofAMPs against them.