Differential Stability of Aurein 1.2 Pores in Model Membranes of Two Probiotic Strains

Abstract

Aurein 1.2 is an antimicrobial peptide from the skin secretion of an Australian frog. In the previous experimental work, we reported a differential action of aurein 1.2 on two probiotic strains Lactobacillus delbrueckii subsp. bulgaricus (CIDCA 331) and Lactobacillus delbrueckii subsp. lactis (CIDCA 133). The differences found were attributed to the bilayer compositions. Cell cultures and CIDCA 331-derived liposomes showed higher susceptibility than the ones derived from the CIDCA 133 strain, leading to content leakage and structural disruption. Here, we used molecular dynamics simulations to explore these systems at the atomistic level. We hypothesize that if the antimicrobial peptides organized themselves to form a pore, it will be more stable in membranes that emulate the CIDCA 331 strain than in those of the CIDCA 133 strain. To test this hypothesis, we simulated preassembled aurein 1.2 pores embedded into bilayer models that emulate the two probiotic strains. It was found that the general behavior of the systems depends on the composition of the membrane rather than the preassemble system characteristics. Overall, it was observed that aurein 1.2 pores are more stable in the CIDCA 331 model membranes. This fact coincides with the high susceptibility of this strain against antimicrobial peptide. In contrast, in the case of the CIDCA 133 model membranes, peptides migrate to the water−lipid interphase, the pore shrinks, and the transport of water through the pore is reduced. The tendency of glycolipids to make hydrogen bonds with peptides destabilizes the pore structures. This feature is observed to a lesser extent in CIDCA 331 due to the presence of anionic lipids. Glycolipid transverse diffusion (flip-flop) between monolayers occurs in the pore surface region in all the cases considered. These findings expand our understanding of the antimicrobial peptide resistance properties of probiotic strains.

A Global Review on Short Peptides: Frontiers and Perspectives

“…It is hard to access with enhanced MD techniques or applying an electric field. Combining CG [ 203 ] and atomistic [ 204 ] level MD simulations could be used to broadly sample the phase space. Thus, different initial conditions could help to explore this space.…”

“…Thus, different initial conditions could help to explore this space. For instance, pre-assembled pores embbebed in lipid bilayers could bring information on their stability dependence with the bilayer lipid composition [ 204 ].…”

Transient Aurein 1.2 pores in prokaryotic model bilayers explored by coarse-grain molecular dynamics simulations: as glycolipid content increases, pore lifetime decreases

“…These results were also extended to liposomes derived from lipid extracts of these two strains, where the liposomes with high amount of glycolipids were refractory to the action of aurein in fluorescence release experiments (Szymanowski et al ., 2019). The resistance showed by this strain was also studied by MD simulations, where the stability of pre-formed pore structures was evaluated, with equivalent results (Balatti et al ., 2020).…”

Dynorphin A induces membrane permeabilization by formation of proteolipidic pores. Insights from electrophysiology and computational simulations

“…Computational biophysics is becoming an important tool for the study of pore forming potential of peptides in bilayers because it helps visualizing and understanding molecular details [33] . Current computational developments in lipid parameters and force fields [34] , [35] , and combination of coarse grain and all-atom simulations to overcome computational costs [36] , are being implemented to expand our knowledge on peptide-lipid interactions, pore nature and organization, and stability of the complexes, to gain insight into peptide-induced membrane perturbation effects [37] .…”