Lipid-specific membrane activity of human β-defensin-3

被引:40
作者
Böhling, A
Hagge, SO
Roes, S
Podschun, R
Sahly, H
Harder, J
Schröder, JM
Grötzinger, J
Seydel, U
Gutsmann, T
机构
[1] Res Ctr Borstel, Leibniz Ctr Med & Biosci, Dept Immunochem & Biochem Microbiol, D-23845 Borstel, Germany
[2] Univ Hosp Schleswig Holstein, Dept Med Microbiol & Virol, D-24105 Kiel, Germany
[3] Univ Hosp Schleswig Holstein, Clin Res Unit, Dept Dermatol, D-24105 Kiel, Germany
[4] Univ Kiel, Dept Biochem, D-24098 Kiel, Germany
关键词
D O I
10.1021/bi052026e
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:5663 / 5670
页数:8
相关论文
共 57 条
[1]   The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface [J].
Bals, R ;
Wang, XR ;
Zasloff, M ;
Wilson, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (16) :9541-9546
[2]   HBD-1 - A NOVEL BETA-DEFENSIN FROM HUMAN PLASMA [J].
BENSCH, KW ;
RAIDA, M ;
MAGERT, HJ ;
SCHULZKNAPPE, P ;
FORSSMANN, WG .
FEBS LETTERS, 1995, 368 (02) :331-335
[3]   Films built by depositing successive monomolecular layers on a solid surface [J].
Blodgett, KB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1935, 57 (01) :1007-1022
[4]   A study of host defence peptide β-defensin 3 in primates [J].
Boniotto, M ;
Antcheva, N ;
Zelezetsky, I ;
Tossi, A ;
Palumbo, V ;
Falzacappa, MVV ;
Sgubin, S ;
Braida, L ;
Amoroso, A ;
Crovella, S .
BIOCHEMICAL JOURNAL, 2003, 374 :707-714
[5]   New insights into the mechanism of action of lantibiotics -: diverse biological effects by binding to the same molecular target [J].
Brötz, H ;
Sahl, HG .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2000, 46 (01) :1-6
[6]  
COCIANCICH S, 1993, J BIOL CHEM, V268, P19239
[7]   Optimization of the antimicrobial activity of magainin peptides by modification of charge [J].
Dathe, M ;
Nikolenko, H ;
Meyer, J ;
Beyermann, M ;
Bienert, M .
FEBS LETTERS, 2001, 501 (2-3) :146-150
[8]   β-defensins:: Endogenous antibiotics of the innate host defense response [J].
Diamond, G ;
Bevins, CL .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1998, 88 (03) :221-225
[9]   The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense [J].
Elsbach, P .
JOURNAL OF LEUKOCYTE BIOLOGY, 1998, 64 (01) :14-18
[10]   DEFENSINS PROMOTE FUSION AND LYSIS OF NEGATIVELY CHARGED MEMBRANES [J].
FUJII, G ;
SELSTED, ME ;
EISENBERG, D .
PROTEIN SCIENCE, 1993, 2 (08) :1301-1312