Lipid-Specific Membrane Activity of Human -Defensin-3
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文摘
Defensins represent a major component of innate host defense against bacteria, fungi, andenveloped viruses. One potent defensin found, e.g., in epithelia, is the polycationic human -defensin-3(hBD3). We investigated the role of the lipid matrix composition, and in particular the presence of negativelycharged lipopolysaccharides (LPS) from sensitive (Escherichia coli, Salmonella enterica serovar Minnesota)or resistant (Proteus mirabilis) Gram-negative bacteria or of the zwitterionic phospholipids of humancells, in determining the action of polycationic hBD3 on the different membranes, and related to theirbiological activity. The main focus was directed on data derived from electrical measurements on areconstitution system of the OM as a planar asymmetric bilayer composed on one side of LPS and on theother of a phospholipid mixture. Our results demonstrate that the antimicrobial activity and the absenceof cytotoxicity can be explained by the lipid-specificity of the peptide. A clear correlation between theseaspects of the biological activity of hBD3 and its interaction with lipid matrices could be found. In particular,hBD3 could only induce lesions in those membranes resembling the lipid composition of the OM ofsensitive bacterial strains. The permeation through the membrane is a decisive first step for the biologicalactivity of many antimicrobial peptides. Therefore, we propose that the lipid-specificity of hBD3 as wellas some other membrane-active antimicrobial peptides is important for their activity against bacteria ormammalian cells.

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