NISIN-Z, MUTANT NISIN-Z AND LACTICIN-481 INTERACTIONS WITH ANIONIC LIPIDS CORRELATE WITH ANTIMICROBIAL ACTIVITY - A MONOLAYER STUDY

Monomolecular layers of lipids at the air/water interface have been us ed as a model membrane to study membrane interactions of the lantibiot ic nisin. The natural lantibiotics nisin A and nisin Z proved to have a high affinity for the anionic lipids phosphatidylglycerol and bis(ph osphatidyl)glycerol (cardiolipin). The interaction with zwitterionic p hopholipids or neutral lipids is very low at surface pressures higher than 32 mN/m. Nisin, nisin mutants and lacticin 481 show a remarkable correlation between antimicrobial activity and anionic lipid interacti on. The results indicate that primarily the N-terminal part (residues 1-22) penetrates into the lipid phase. Reduction of the flexibility at positions 20-21 has a negative effect on monolayer interaction and ac tivity. The C-terminal part is probably responsible for ionic interact ions of nisin in monomeric or oligomeric form with anionic lipids. In mixtures of anionic and zwitterionic lipids maximal interactions are f ound at approximately 70 mol/100 mol anionic lipid. Gram-positive bact eria, which form the main target for nisin, are characterized by a hig h content of anionic lipids in the membrane. Monolayers formed of lipi d extracts of bacteria sensitive to nisin were more strongly penetrate d than those of bacteria relatively insensitive to nisin.