Interactions of antibiotics of the iturin group with human erythrocytes.
The peptidolipid antibiotics, iturin A and bacillomycin L have a disrupting effect on erythrocyte membrane leading to a simultaneous release of K+ ions and hemoglobin. The formation of ghosts is accompanied by a partial solubilisation of lipid components. Binding experiments with radioactive antibiotics show that about 7 X 10(7) molecules of iturin A and 4 X 10(7) molecules of bacillomycin L are bound to one erythrocyte at the concentration giving 100% hemolysis. This concentration is reduced by about 20% after treatment of erythrocytes by phospholipase A2. Scatchard plots show that the affinity for erythrocyte membrane is higher with bacillomycin L than with iturin A. This difference is probably correlated to the differences in their peptide moieties. The substitution of tyrosyl residue leads to a ten-fold increase of the concentrations giving 100% hemolysis, probably due to a low distribution coefficient of derivatives between the membrane and the solvent. This result and the humped Scatchard curves obtained with both antibiotics may be related to the self-association of the compounds in aqueous solutions.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000097:blood; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011188:Potassium / Q000097:blood; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008563:Membrane Lipids; D010455:Peptides; D010456:Peptides, Cyclic; D012710:Serum Albumin, Bovine; D014443:Tyrosine; C013579:iturin A; C015015:bacillomycin L; D010741:Phospholipases A; D054467:Phospholipases A2; D011188:Potassium