X-ray studies on the interaction of the antimicrobial peptide gramicidin S with microbial lipid extracts: evidence for cubic phase formation

• Published in: Biochimica et biophysica acta Vol. 1468; no. 1; pp. 213 - 230
• Main Authors: Staudegger, Erich, Prenner, Elmar J., Kriechbaum, Manfred, Degovics, Gábor, Lewis, Ruthven N.A.H., McElhaney, Ronald N., Lohner, Karl
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 29.09.2000
• Subjects: Acholeplasma - drug effects; Acholeplasma - metabolism; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial peptide; Crystallization; Escherichia coli - drug effects; Escherichia coli - metabolism; Gramicidin - chemistry; Gramicidin - pharmacology; Gramicidin S; Lipid Bilayers - chemistry; Lipid–peptide interaction; Magnetic Resonance Spectroscopy; Membrane Lipids - chemistry; Microbial lipid; Models, Molecular; Non-lamellar phase; Phospholipid; Temperature; X-Ray Diffraction - methods; Phospholipid; Gramicidin S; Microbial lipid; Lipid–peptide interaction; Antimicrobial peptide; Non-lamellar phase
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/S0005-2736(00)00260-1

We have investigated the effect of the interaction of the antimicrobial peptide gramicidin S (GS) on the thermotropic phase behavior of model lipid bilayer membranes generated from the total membrane lipids of Acholeplasma laidlawii B and Escherichia coli. The A. laidlawii B membrane lipids consist primarily of neutral glycolipids and anionic phospholipids, while the E. coli inner membrane lipids consist exclusively of zwitterionic and anionic phospholipids. We show that the addition of GS at a lipid-to-peptide molar ratio of 25 strongly promotes the formation of bicontinuous inverted cubic phases in both of these lipid model membranes, predominantly of space group Pn3m. In addition, the presence of GS causes a thinning of the liquid-crystalline bilayer and a reduction in the lattice spacing of the inverted cubic phase which can form in the GS-free membrane lipid extracts at sufficiently high temperatures. This latter finding implies that GS potentiates the formation of an inverted cubic phase by increasing the negative curvature stress in the host lipid bilayer. This effect may be an important aspect of the permeabilization and eventual disruption of the lipid bilayer phase of biological membranes, which appears to be the mechanism by which GS kills bacterial cells and lysis erythrocytes.