Lipid-specific membrane activity of human beta-defensin-3.
Defensins represent a major component of innate host defense against bacteria, fungi, and enveloped viruses. One potent defensin found, e.g., in epithelia, is the polycationic human beta-defensin-3 (hBD3). We investigated the role of the lipid matrix composition, and in particular the presence of negatively charged lipopolysaccharides (LPS) from sensitive (Escherichia coli, Salmonella enterica serovar Minnesota) or resistant (Proteus mirabilis) Gram-negative bacteria or of the zwitterionic phospholipids of human cells, in determining the action of polycationic hBD3 on the different membranes, and related to their biological activity. The main focus was directed on data derived from electrical measurements on a reconstitution system of the OM as a planar asymmetric bilayer composed on one side of LPS and on the other of a phospholipid mixture. Our results demonstrate that the antimicrobial activity and the absence of cytotoxicity can be explained by the lipid-specificity of the peptide. A clear correlation between these aspects 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 of sensitive bacterial strains. The permeation through the membrane is a decisive first step for the biological activity of many antimicrobial peptides. Therefore, we propose that the lipid-specificity of hBD3 as well as some other membrane-active antimicrobial peptides is important for their activity against bacteria or mammalian cells.
Böhling
Arne
A
Department of Immunochemistry and Biochemical Microbiology, Leibniz-Center for Medicine and Biosciences, Research Center Borstel, Parkallee 1-40, D-23845 Borstel, Germany.
Hagge
Sven O
SO
Roes
Stefanie
S
Podschun
Rainer
R
Sahly
Hany
H
Harder
Jürgen
J
Schröder
Jens-Michael
JM
Grötzinger
Joachim
J
Seydel
Ulrich
U
Gutsmann
Thomas
T
D004553:Electric Conductivity; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D018625:Microscopy, Atomic Force; D011513:Proteus mirabilis / Q000187:drug effects; D019779:Salmonella enterica / Q000187:drug effects; D023083:beta-Defensins / Q000737:chemistry* / Q000502:physiology
C422950:DEFB103A protein, human; D008051:Lipid Bilayers; D008563:Membrane Lipids; D023083:beta-Defensins