Mechanism of lantibiotic-induced pore-formation

Nisin and other lantibiotics have a bacteriocidal effect against Gram-positive bacteria, and also inhibit the outgrowth of bacterial spores. The bacteriocidal effect appears to be due to the formation of pores in the bacterial membrane. In the absence of anionic membrane phospholipids, the lantibiotic nisin acts as an anion selective carrier. In the presence of anionic phospholipids, nisin forms nonselective, transient, multi-state pores in cells, proteoliposomes, liposomes and black lipid membranes. Pore formation involves distinct steps. First, nisin associates tightly with the anionic membrane surface leading to a high local concentration. This results in a disturbance of the lipid dynamics near the phospholipid polar head group-water interface, and an immobilization of lipids. In the presence of a transmembrane electrical potential above the threshold level, the molecules reorient, presumably as an aggregate, from a surface-bound into a membrane-inserted configuration. Go-insertion of bound, anionic phospholipids results in bending of the lipid surface giving rise to a wedge-like, nonspecific, water-filled pore.