Kinetic and Structural Aspects of the Permeabilization of Biological and Model Membranes by Lichenysin

Abstract

The various lichenysins produced by Bacillus licheniformis are anionic surfactants with interesting properties. Here it is shown that lichenysin caused hemolysis of human erythrocytes, which varied with lichenysin concentration in a sigmoidal manner. The release of K(+) from red blood cells induced by lichenysin preceded the leakage of hemoglobin, and in addition, hemolysis could be impeded by the presence of compounds in the external medium having a size larger than that of PEG 3350, indicating a colloid-osmotic mechanism for hemolysis. Lichenysin also caused permeabilization of model phospholipid membranes, which was a slow process with an initial lag period of 10-20 s observed for all lichenysin concentrations. A high cholesterol ratio in the membrane decreased the extent of leakage as compared to that of pure POPC, whereas at lower ratios the effect of cholesterol was the opposite, enhancing the extent of leakage. POPE was found to decrease the extent of leakage at all the concentrations assayed, and inclusion of DPPC resulted in a considerable increase in CF leakage extent. From this scenario it was concluded that lipid membrane composition plays a role in the target membrane selectivity of lichenysin. Molecular dynamics simulations indicated that lichenysin is well distributed along the bilayer, and Na(+) ions can penetrate inside the bilayer through the lichenysin molecules. The presence of lichenysin in the membrane increases the permeability of the membrane to hydrophilic molecules facilitating its flux across the lipid palisade. The results presented in this work contribute to understanding the molecular mechanisms that explain the biological actions of lichenysin related to biomembranes.

Interaction of the Lipopeptide Biosurfactant Lichenysin with Phosphatidylcholine Model Membranes

“…The main similarity between these lipid molecules and Lichenysin, with its amino acid ring, is probably their bulky shapes, making it difficult to fit in the hexagonal packing of the hydrocarbon chains of the phosphatidylcholines in the gel phase and thus better accommodating into fluid domains. This preferential partitioning into fluid domains is of biological relevance because Lichenysin has been shown to induce permeabilization of model and biological membranes in the fluid state . A similar effect has been recently described for the interaction of ultrashort lipopeptides with negatively charged phospholipid membranes, indicating that this behavior could be more general as far as lipopeptides are concerned.…”

“…DPPC topology file was obtained from Chiu and coworkers . The Lichenysin molecule (Figure ) and the molecular dynamics simulations were carried out as we have described recently . The pure DPPC lipid bilayer was composed of two monolayers containing 36 DPPC molecules per monolayer hydrated with a total of 3349 molecules of water.…”

Biosurfactants synthesized by endophytic Bacillus strains as control of Moniliophthora perniciosa and Moniliophthora roreri

“…The cocoa endophytic strain DS03 showed the highest antifungal activity; this strain caused both phytopathogens' swelling hyphae due to biosurfactant reaction over the fungus cell wall. In connection with this, Coronel-León et al (2016c) mentioned that the mechanism of action lipopeptides from Bacillus was based on osmotic perturbation, including ion-pore formation; according to this information, results suggest that liquid accumulated in the periphery of the hyphae due to increased permeability of the cell membrane (Figure 6). These results are consistent with those published by Mnif et al (2015) who described the loss of the granulation and fragmentation of hyphal mycelia of the pathogenic fungi Ralstonia bataticola when treated with antifungal metabolites produced by B. subtilis SPB1.…”

Lichenysin-geminal amino acid-based surfactants: Synergistic action of an unconventional antimicrobial mixture

“…Recently, lichenysin interaction with a DPPC-model membrane was demonstrated, indicating that lichenysin penetrates inside the membrane [39]. Despite the low percentage of affected cells detected by bacterial count and by flow cytometry the present work assess the synergistic role of lichenysin, at low concentration, in the antimicrobial activity of the binary system with C3(LA)2 .…”