Interaction of polymyxin B nonapeptide with anionic phospholipids.
The interaction of polymyxin B nonapeptide (PMBN) and polymyxin B (PMB) with the anionic phospholipids phosphatidylserine (PS), dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidic acid (DPPA), and 1:1 mixtures (w/w) of DPPA and distearoylphosphatidylcholine (DSPC) was studied by calorimetry, electron spin resonance, and fluorescence spectrometry, electron microscopy, and fusion and leakage assays. The phase transition temperatures of DPPA and DPPG were very similar when bound to PMB or PMBN, indicating that the lipids are in a similar state when bound to the cationic peptides. Both PMB and PMBN caused the interdigitation of DPPG bilayers, suggesting that the penetration of hydrophobic side chains from a peptide bound electrostatically on the surface is sufficient to induce this phenomenon. Stopped-flow experiments revealed that PMBN and PMB induced the fusion of small unilamellar PS and large unilamellar DPPA-DSPC vesicles. The aggregation of vesicles was found to be diffusion-controlled process; the subsequent fusion took place with a frequency of 10(2)-(5 X 10(2] s-1 for small vesicles and 1-100 s-1 for large vesicles. The freeze-fracture replicas of the PMB-treated vesicles displayed 12-50-nm depressions on several superimposed bilayers, indicating the formation of stable lipid-PMB domains. Since the incubation with PMBN produced similar depressions only if the specimens were fixed, PMBN-induced domain formation seems to be a reversible rapid process. The differences in the phospholipid-peptide interactions are correlated with the differences in the physiological action of the antibiotic PMB and the nonbactericidal PMBN on the cell envelope of Gram-negative bacteria.
D002152:Calorimetry, Differential Scanning; D004578:Electron Spin Resonance Spectroscopy; D005614:Freeze Fracturing; D008081:Liposomes; D008854:Microscopy, Electron; D008954:Models, Biological; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D010743:Phospholipids; D011112:Polymyxin B / Q000031:analogs & derivatives; D011113:Polymyxins; D013329:Structure-Activity Relationship
D008081:Liposomes; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D010743:Phospholipids; D011113:Polymyxins; C031599:dipalmitoylphosphatidic acid; C038934:polymyxin B nonapeptide; C010942:1,2-distearoyllecithin; D011112:Polymyxin B; C030345:1,2-dipalmitoylphosphatidylglycerol