Aurein 1.2 and Maculatin 1.1 antimicrobial action over complex bilayers. A multidisciplinary approach using both coarse-grained and atomistic molecular dynamics simulations

AMBROGGIO EE; FIDELIO GD; SZYMANOWSKI F; PÉREZ PF; PICKHOLZ M.; BALATTI GE; GÓMEZ-ZAVAGLIA A; MARTINI FM

varadero

Workshop; Iubmb/iupab advanced school and workshop 2018; 2018

The antimicrobial peptides (AMPs) are molecules that exert their action mainly against bacteria, among other external agents. It was suggested in the literature that AMPs act by increasing the permeability of the membrane after an early peptide-lipid interaction. Among AMPs, two peptides obtained from anuran amphibians, the aurein 1.2 and the maculatin 1.1 exhibit a well-proven lytic activity and, previously, we shed light about the molecular mechanism by which they damage biomembranes by combined computational and experimental approaches.At the same time, the Lactobacillus delbrueckii subsp. lactis (CIDCA133) and the L. delbrueckii subsp. bulgaricus (CIDCA331) are bacterial strains that exhibit different susceptibility to the action of human AMPs, being CIDCA133 more resistant than CIDCA331. Our recent experiments showed that the differential susceptibility of the strains can be extended to both aurein and maculatin. Considering the membrane composition as a key aspect of the CIDCA331 resistance to AMPs, we carried out extensive Molecular Dynamics (MD) to understand the aurein and maculatin interactions with these membranes and the relationship with the resistance properties. Due to the size of the bilayer systems and the time scales required, we used the MARTINI coarse-grain force field. Additional atomistic simulations by using CHARMM36 helped us to study specific aspects of the peptide-lipid interactions.The results exhibit differential interactions and molecular behavior of both AMPs on CIDCA133 and CIDCA331 model membranes, in good agreement with the previous observations. The combined coarse-grain and atomistic approaches can elucidate specific molecular factors that allow certain lipid mixes to resist or diminish the effects of AMPs against them.