Development Of New Antimicrobial Peptides And Their Interaction With Model Membranes


The uprising resistance of pathogenic bacteria against treatments with conventional antibiotics is a world wide problem which led to an acute search for alternatives. One class of promising molecules are naturally occurring antimicrobial peptides, which belong to the innate immune system of many different species. These peptides act by direct physical interaction with the membranes of their target cells and can thereby be distinguished from antibiotics. Another important feature of antimicrobial peptides is their high affinity for bacteria and fungi in contrast to mammalian cells. In our work we tested the activity of the synthetic antimicrobial peptide NK-CS and derivatives thereof against Escherichia coli (Gram negative) and Staphylococcus carnosus (Gram positive) as well as the hemolytic properties against human red blood cells. In parallel we investigated the interaction of the peptides with different model membranes by small angle X-ray scattering. This combination should give an indication of the structure-function relationship of the peptide-lipid-system. We found NK-CS to be a very potent antimicrobial peptide, while none of the derivatives showed improved antibacterial selectivity and activity. Structural characterization of the interaction between the peptide and model membranes revealed that for all tested peptides the inverse hexagonal phase transition of phosphatidylethanolamine lipids was altered in a specific manner which can be correlated with the activity of the peptides. This phase transition temperature was increased by the peptides meaning the promotion of a positive curvature of the membranes. We assume that, as it was found for Magainins, this curvature finally leads to the disruption of the model membranes.
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