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 investigated. The threshold concentrations of lantibiotics to form ion channels and to disintegrate planar lipid bilayers were determined. It was found that nisin was able to form ion channels of conductance in the range from 2 to 600 pS at a concentration more than 40 mu M in both negatively charged lipid bilayers, including a lipopolysaccharide of the outer membranes of gram-negative bacteria, Kdo(2)-lipid A, and cardiolipin-containing membranes. The results obtained suggest that in model lipid membranes lacking lipid II, a precursor of peptidoglycan of gram-positive bacteria, Kdo(2)-lipid A and cardiolipin can play the role of specific nisin receptors. 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 an amplitude of 5 to 30 and 50 to 900 pS in membranes made from phosphatidylethanolamine and cardiolipin-enriched bilayers, respectively. Based on the obtained results, it was concluded 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 inducing negative spontaneous curvature of lipid monolayers.