The Dependence of the Channel-Forming Ability of Lantibiotics on the Lipid Composition of the Membranes

The role of various membrane components, phospholipids and lipopolysaccharides, in the formation and functioning of ion channels formed by lantibiotics of class A, nisin, and class B, cinnamycin and duramycin, was studied. Threshold concentrations of the tested lantibiotics were determined that cause ion channel formation and destruction of planar lipid bilayers. It was found that nisin was able to form ion channels with a conductance in the range from 2 to 600 pS at a concentration of more than 40 mu M both in negatively charged lipid bilayers containing a specific adjuvant of gram-negative bacterial membranes, Kdo(2)-lipid A, and in cardiolipin-containing membranes. The obtained results allowed suggesting that in model lipid membranes without lipid II, a precursor of peptidoglycan of gram-positive bacteria, which is a specific receptor of nisin, its role can be performed by Kdo(2)-lipid A and cardiolipin. It was found that cinnamycin and its close analogue duramycin at concentrations of 1.5-3 mu M induced step-like current fluctuations corresponding to the functioning of single ion channels with amplitudes from 5 to 30 pS and from 50 to 900 pS in membranes of phosphatidylethanolamine and cardiolipin-enriched bilayers, respectively. Based on the results obtained, we conclude that the channel-forming ability of cinnamycin and duramycin depends on the presence in the membrane of lipids prone to the formation of inverted hexagonal phases and the induction of spontaneous negative curvature in lipid monolayers.