Antimicrobial activities of heparin-binding peptides.
Antimicrobial peptides are effector molecules of the innate immune system. We recently showed that the human antimicrobial peptides alpha-defensin and LL-37 bind to glycosaminoglycans (heparin and dermatan sulphate). Here we demonstrate the obverse, i.e. structural motifs associated with heparin affinity (cationicity, amphipaticity, and consensus regions) may confer antimicrobial properties to a given peptide. Thus, heparin-binding peptides derived from laminin isoforms, von Willebrand factor, vitronectin, protein C inhibitor, and fibronectin, exerted antimicrobial activities against Gram-positive and Gram-negative bacteria. Similar results were obtained using heparin-binding peptides derived from complement factor C3 as well as consensus sequences for heparin-binding (Cardin and Weintraub motifs). These sequence motifs, and additional peptides, also killed the fungus Candida albicans. These data will have implications for the search for novel antimicrobial peptides and utilization of heparin-protein interactions should be helpful in the identification and purification of novel antimicrobial peptides from complex biological mixtures. Finally, consensus regions may serve as templates for de novo synthesis of novel antimicrobial molecules.
Department of Medical Microbiology, Dermatology and Infection, Section for Dermatology, Lund University, Biomedical Center, Sweden.
Emma
E
Andersson
Victoria
V
Rydengård
Andreas
A
Sonesson
Matthias
M
Mörgelin
Lars
L
Björck
Artur
A
Schmidtchen
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D003176:Complement C3 / Q000737:chemistry; D016384:Consensus Sequence; D013293:Enterococcus faecalis / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D011869:Radioligand Assay
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D003176:Complement C3; D006493:Heparin