Mechanistic studies of lantibiotic-induced permeabilization of phospholipid vesicles.
Nisin is a cationic polycyclic bacteriocin secreted by some lactic acid 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 phosphatidylglycerol (PG). Nisin induces the release of 6-carboxyfluorescein and other small anionic fluorescent dyes from PC liposomes in a delta psi-stimulated 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 reconstituted with PG, with a threshold delta psi requirement of about -100 mV. Nisin associates with the anionic surface of PG liposomes and disturbs the lipid dynamics near the phospholipid polar head group-water interface. Further studies with a novel cationic lantibiotic, epilancin K7, indicate that this molecule penetrates into the hydrophobic carbon 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 absence of anionic phospholipids. In vivo, however, this activity is likely to be prevented by electrostatic interactions with anionic lipids of 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 from a surface-bound into a membrane-inserted configuration.
Department of Microbiology, University of Groningen, Haren, The Netherlands.
A J
AJ
Driessen
H W
HW
van den Hooven
W
W
Kuiper
M
M
van de Kamp
H G
HG
Sahl
R N
RN
Konings
W N
WN
Konings
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins; D001692:Biological Transport; D005456:Fluorescent Dyes; D008081:Liposomes / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009561:Nisin / Q000494:pharmacology*; D010455:Peptides; D010713:Phosphatidylcholines / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D005456:Fluorescent Dyes; D008081:Liposomes; D010455:Peptides; D010713:Phosphatidylcholines; C092251:epilancin K7; D009561:Nisin