Structural rearrangement of model membranes by the peptide antibiotic NK-2.
We have developed a novel alpha-helical peptide antibiotic termed NK-2. It efficiently kills bacteria, but not human cells, by membrane destruction. This selectivity could be attributed to the different membrane lipid compositions of the target cells. To understand the mechanisms of selectivity and membrane destruction, we investigated the influence of NK-2 on the supramolecular aggregate structure, the phase transition behavior, the acyl chain fluidity, and the surface charges of phospholipids representative for the bacterial and the human cell cytoplasmic membranes. The cationic NK-2 binds to anionic phosphatidylglycerol liposomes, causing a thinning of the membrane and an increase in the phase transition temperature. However, this interaction is not solely of electrostatic but also of hydrophobic nature, indicated by an overcompensation of the Zeta potential. Whereas NK-2 has no effect on phosphatidylcholine liposomes, it enhances the fluidity of phosphatidylethanolamine acyl chains and lowers the phase transition enthalpy of the gel to liquid cristalline transition. The most dramatic effect, however, was observed for the lamellar/inverted hexagonal transition of phosphatidylethanolamine which was reduced by more than 10 degrees C. Thus, NK-2 promotes a negative membrane curvature which can lead to the collapse of the phosphatidylethanolamine-rich bacterial cytoplasmic membrane.
Willumeit
Regine
R
GKSS Research Center, Geesthacht, Germany.
Kumpugdee
Mont
M
Funari
Sérgio S
SS
Lohner
Karl
K
Navas
Beatriz Pozo
BP
Brandenburg
Klaus
K
Linser
Sebastian
S
Andrä
Jörg
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D017434:Protein Structure, Tertiary
D000900:Anti-Bacterial Agents; D008081:Liposomes; D010455:Peptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; C475945:peptide NK-2; C483858:phosphatidylethanolamine