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Susceptibility of sheep, human, and pig erythrocytes to haemolysis by the antimicrobial peptide Modelin 5

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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.

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Authors and Affiliations

  1. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK

    Sarah R. Dennison

  2. London South Bank University, 103 Borough Road, London, SE1 0AA, UK

    David A. Phoenix

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  1. Sarah R. Dennison
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  2. David A. Phoenix
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Correspondence to David A. Phoenix.

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Dennison, S.R., Phoenix, D.A. Susceptibility of sheep, human, and pig erythrocytes to haemolysis by the antimicrobial peptide Modelin 5. Eur Biophys J 43, 423–432 (2014). https://doi.org/10.1007/s00249-014-0974-9

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  • DOI: https://doi.org/10.1007/s00249-014-0974-9

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