MECHANISTIC STUDIES OF LANTIBIOTIC-INDUCED PERMEABILIZATION OF PHOSPHOLIPID-VESICLES

Nisin is a cationic polycyclic bacteriocin secreted by some lactic aci d bacteria. Nisin has previously been shown to permeabilize Liposomes. The interaction of nisin was analyzed with liposomes prepared of the zwitterionic phosphatidylcholine (PC) and the anionic phosphatidylglyc erol (PG). Nisin induces the release of 6-carboxyfluorescein and other small anionic fluorescent dyes from: PC Liposomes in;a Delta psi-stim ulated manner, and not that of neutral and cationic fluorescent dyes. This activity is blocked in PG liposomes. Nisin, however, efficiently dissipates the Delta psi in cytochrome c oxidase proteoliposomes recon stituted with PG, with a threshold Delta psi, requirement of about -10 0 mV. Nisin associates with the anionic surface of PG liposomes and di sturbs the lipid dynamics near the phospholipid polar head group-water interface. Further studies with a novel cationic lantibiotic, epilanc in K7, indicate that this molecule penetrates into the hydrophobic car bon region of the Lipid bilayer upon the imposition of a Delta psi. It is concluded that nisin acts as an anion-selective carrier in the abs ence of anionic phospholipids. In vivo, however, this activity is like ly to be prevented by electrostatic interactions with anionic lipids o f the target membrane. It is suggested that pore formation by cationic (type A) lantibiotics involves the local perturbation of the bilayer structure and a Delta psi-dependent reorientation of these molecules f rom a surface-bound into a membrane-inserted configuration.