Study of Aurein 1.2 and Maculatin 1.1 antimicrobial peptides action over complex bilayers. A multidisciplinary approach using both computational and experimental methods

BALATTI, GALO EZEQUIEL; AMBROGGIO, ERNESTO ESTEBAN; SZYMANOWSKI, F; HUGO, AA; GÓMEZ-ZAVAGLIA, A; PÉREZ, PF; FIDELIO, GERARDO DANIEL; MARTINI, MARIA FLORENCIA; PICKHOLZ, MONICA ANDREA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

The antimicrobial peptides (AMPs) are molecules that exert theiraction mainly against bacteria, among other pathogens. It was sug-gested in the literature that AMPs act by increasing the permeabil-ity of the membrane after an early interaction with the membrane.Among AMPs, two peptides obtained from australian frogs, the aure-in 1.2 and the maculatin 1.1 exhibit structural features representa-tive of α- helical AMPs and a well-proven lytic activity. This behaviorwas captured, both from experiments and computer simulations.Lactobacillus delbrueckii subsp. lactis (strain CIDCA133) and L.delbrueckii subsp. bulgaricus (strain CIDCA331) showed differentsusceptibility to the action of human AMPs (β-defensines). Sincethe membrane composition of each strain is substancially different,we studied here the effect of both AMPs: aurein and maculatin onliposomes made with lipids extracted from both strains, carrying outseveral liposome content leakage experiments. By the other hand,aiming to understand the molecular mechanism of aurein and mac-ulatin interaction with membranes, we carried out extensive Molecu-lar Dynamics (MD) simulations. In order to mimic the membrane lipidcomposition of both strains, and due to the size of the bilayer sys-tems and the time scales required, we used the MARTINI coarseg-rain force field.Our results show significant differences in the interaction of thestudied AMPs with each strain: both experimental and MD studieslet us propose differential models in each case. While maculatin candestabilize the membrane inducing membrane curvature, aurein ex-hibits surfactant properties, acting as an amphiphilic molecule, andfavoring a pore formation. Moreover, we found significant differenc-es respect the susceptibility of strains CIDCA133 and CIDCA331.In the present work, we combined computational methods comple-mented with experimental techniques to get insights on the partic-ular AMPs ways of action and the resistance of certain membranesagainst them.Keywords: antimicrobial peptides, molecular dynamics, coarse-grain, probiotics, complex membranes