The cooperative behaviour of antimicrobial peptides in model membranes

Abstract

A systematic analysis of the hypothesis of the antimicrobial peptides' (AMPs) cooperative action is performed by means of full atomistic molecular dynamics simulations accompanied by circular dichroism experiments. Several AMPs from the aurein family (2.5,2.6, 3.1), have a similar sequence in the first ten amino acids, are investigated in different environments including aqueous solution, trifluoroethanol (TFE), palmitoyloleoylphosphatidylethanolamine (POPE), and palmitoyloleoylphosphatidylglycerol (POPG) lipid bilayers. It is found that the cooperative effect is stronger in aqueous solution and weaker in TFE. Moreover, in the presence of membranes, the cooperative effect plays an important role in the peptide/lipid bilayer interaction. The action of AMPs is a competition of the hydrophobic interactions between the side chains of the peptides and the hydrophobic region of lipid molecules, as well as the intra peptide interaction. The aureins 2.5-COOH and 2.6-COOH form a hydrophobic aggregate to minimize the interaction between the hydrophobic group and the water. Once that the peptides reach the water/lipid interface the hydrophobic aggregate becomes smaller and the peptides start to penetrate into the membrane. In contrast, aurein 3.1-COOH forms only a transient aggregate which disintegrates once the peptides reached the membrane, and it shows no cooperativity in membrane penetration.

Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity

“…After the simulation had run for 100 ns all the peptides were interacting with the lipids regardless of the composition of the membrane. In general, the temporin B peptides showed deeper insertion in POPG membranes, as observed previously, 42 compared with POPE/POPG membranes, with contact and insertion beginning at the N-terminus in all cases. The temporin B peptides were also frequently self-associated ( Fig.…”

Modulating charge-dependent and folding-mediated antimicrobial interactions at peptide–lipid interfaces

“…Fluorinated alcohols promote intramolecular hydrogen bonding by excluding water from the solute, which they achieve by encompassing peptides in a hydrophobic “matrix” and lowering the dielectric constant. Thus, the secondary structure observed in the presence of TFE would correspond to that of the peptide alone defined by the helical propensity of its backbone (Buck 1998; Lee et al 1999; Roccatano et al 2002; Wang et al 2014). As expected, upon excitation at 280 nm, both peptides exhibited fluorescence emission maxima at 303 nm.…”

Parallel evolution of frog antimicrobial peptides produces identical conformations but subtly distinct membrane and antibacterial activities

“…The relaxation delay was 1 s. 2048 data points were recorded in the direct dimension, and either 256 or 512 data points in the indirect dimension. CARA (version 1.9.1.2) and Dynamo software 30,31 were used for the structure calculation. Inter-proton NOEs interactions were used as distance restraints in the structure calculation.…”

“…25 Of these, aurein 2.5 has been studied in some detail. [26][27][28][29][30] Aurein 2.5 also has a strong preference for adopting ordered α-helix conformations in a variety of membrane environments 27,29,30 and strong surface activity was found in both anionic and zwitterionic model membranes. 26 Rana temporaria and Litoria aurea are examples of frogs from, respectively, the Ranidae and Hylidae families.…”