AUREIN 1.2 AND MACULATIN 1.1 ANTIMICROBIAL PEPTIDES ACTION OVER LIPID STRUCTURES: A MULTIDISCIPLINARY STUDY USING BOTH MOLECULAR DYNAMICS SIMULATIONS AND FLUORESCENCE CONFOCAL MICROSCOPY

BALATTI, G. E.; AMBROGGIO, E.; GÓMEZ-ZAVAGLIA, A; PÉREZ, P.F.; FIDELIO, G.D.; MARTINI, M. F.; PICKHOLZ, M.

Santos

Congreso; XLII Brazilian Biophysical Society Congress; 2017

Brazilian Biophysical Society (SBBf)

The antimicrobial peptides (AMPs), as part of the innate immune system, exert theiraction against agents among bacteria, fungi, viruses and eukaryotic parasites. It wassuggested in the literature that AMPs act by increasing the permeability of themembrane after binding it. Among them, two peptides obtained from australian treefrogs, the aurein 1.2 and the maculatin 1.1 exhibit structural features typical of helicalAMPs and a well-proven lytic activity, the key aspect of AMPs [1]. However, themolecular mechanism by which they interact with membranes is still under discussion.On the other hand, the Lactobacillus delbrueckii subsp. lactis (CIDCA133) and the L.delbrueckii subsp. bulgaricus (CIDCA331) showed different susceptibility to the actionof human beta-defensins, being the CIDCA133 resistant against the action of differentAMP such us defensins [3]. The membrane composition of CIDCA133 and CIDCA331is rather different. In this direction, here we studied the effect of both aurein andmaculatin on liposomes made from lipid extracts. In order to study the resistancemechanism in addition to the peptide way of action, we carried out several liposomecontent leakage experiments using fluorescence confocal microscopy and giantunilamellar vesicles (GUVs) prepared from purified bacterial lipids. Furthermore, aimingto understand the molecular mechanism of aurein and maculatin interaction withmembranes, we carried out extensive Molecular Dynamics (MD) simulations. We havechosen a coarse grain approach within the MARTINI force field [2] due to the size ofthe systems under study and the time scales required. We have emulated themembrane lipid composition of CIDCA 331 and CIDCA 133. Our results show that bothpeptides can form different pore-like structures. The differential behavior on thepeptide-membrane interactions of aurein and maculatin is in good agreement withprevious experimental observations [1]. While maculatin can form a pore maintainingthe structure of the bilayer and can induce membrane curvature, aurein exhibitssurfactant properties and this may cause the total membrane destabilization.Thecombined computational and experimental approach has provided insights about theparticular AMPs ways of action and the resistance of certain membranes against them .