Structural rearrangement of model membranes by the peptide antibiotic NK-2

Abstract

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.

The Antimicrobial Peptide NK-2, the Core Region of Mammalian NK-Lysin, Kills Intraerythrocytic Plasmodium falciparum

“…This result may be due to the high molar ratio of NK-2 to annexin V, in addition to annexin V's reversible binding to the RBC surface mentioned before or to a higher affinity to the RBC surface of NK-2 compared to that of annexin V. Moreover, it might be possible that PS is not the only component of the outer layer of the erythrocyte plasma membrane to which NK-2 binds. Other candidates may be phosphatidylethanolamine (PE) (33,43) and phosphatidylgycerol (4,43). It is known that like the case with PS, the amount of PE is also increased in the outer leaflet of the iRBC membrane, whereas the amount of PC is lower compared to that in normal RBC (28).…”

Interaction of an Antimicrobial Peptide with Membranes: Experiments and Simulations with NKCS

“…11 The peptide was found to reduce the transition temperature of the lipid bilayer in a concentration dependent manner by up to 10°C. 15 The replacement of cysteine residue within the NK-2 sequence with a serine (C7S), resulted in a peptide with an improved antibacterial activity referred to as NKCS in the current study. 16 Both peptides are randomly coiled in water and adopt a helical structure upon interaction with the lipid bilayer.…”

The lipid network

“…The role of LPS-but not PG-as a critical partner is further shown for the NK2 peptide-another porcine AMP. Indeed, the weak interaction with PG membranes could not explain the bactericidal activities against E. coli bacteria (Hammer et al 2010;Willumeit et al 2005). Using LPS extracted from E. coli and P. mirabilis, the differences in activity could be identified in the LPS-binding step where the net charge and charge distribution difference of the two LPS was proposed to be responsible for the specific activities (Hammer et al 2010).…”