title: Susceptibility of sheep, human, and pig erythrocytes to haemolysis by the antimicrobial peptide Modelin 5.
abstract: Modelin-5-CONH2, a synthetic antimicrobial peptide, was used to gain an insight into species-selective haemolytic activity. The peptide displayed limited haemolytic activity against sheep (12%), human (2%), and pig (2%) erythrocytes. Our results show that Modelin-5-CONH2 had a disordered structure in the presence of vesicles formed from sheep, human, and pig erythrocyte lipid extract (<26% helical) yet folded to form helices in the presence of a phosphatidylcholine (PC) membrane interface (e.g. >42% in the presence of 1,2-dimyristoyl-sn-glycero-3-phosphocholine). Monolayer studies showed a strong correlation between anionic lipid content and monolayer insertion and lysis inducing surface pressure changes of 9.17 mN m(-1) for 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine compared with PC monolayers, which induced pressure changes of ca. 3 mN m(-1). The presence of cholesterol in the membrane is shown to increase the packing density as the PC:sphingomyelin (SM) ratio increases so preventing the peptide from forming a stable association with the membrane. The data suggests that the key driver for membrane interaction for Modelin-5-CONH2 is the anionic lipid attraction. However, the key factors in the species-specific haemolysis level for this peptide are the differing packing densities which are influenced by the SM:PC:cholesterol ratio.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.forename: David A
authors.initials: DA
authors.lastname: Phoenix
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D017433:Protein Structure, Secondary; D012756:Sheep; D013045:Species Specificity; D013552:Swine
chemical_list: D023181:Antimicrobial Cationic Peptides; C089690:modelin 5