Antimicrobial peptides derived from growth factors.
Growth factors, comprising diverse protein and peptide families, are involved in a multitude of developmental processes, including embryogenesis, angiogenesis, and wound healing. Here we show that peptides derived from HB-EGF, amphiregulin, hepatocyte growth factor, PDGF-A and PDGF-B, as well as various FGFs are antimicrobial, demonstrating a previously unknown activity of growth factor-derived peptides. The peptides killed the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis, as well as the fungus Candida albicans. Several peptides were also active against the Gram-positive S. aureus. Electron microscopy analysis of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. Furthermore, HB-EGF was antibacterial per se, and its epitope GKRKKKGKGLGKKRDPCLRKYK retained its activity in presence of physiological salt and plasma. No discernible hemolysis was noted for the growth factor-derived peptides. Besides providing novel templates for design of peptide-based antimicrobials, our findings demonstrate a previously undisclosed link between the family of growth factors and antimicrobial peptides, both of which are induced during tissue remodelling and repair.
Malmsten
Martin
M
Department of Pharmacy, Uppsala University, Uppsala, SE-751 23, Sweden.
Davoudi
Mina
M
Walse
Björn
B
Rydengård
Victoria
V
Pasupuleti
Mukesh
M
Mörgelin
Matthias
M
Schmidtchen
Artur
A
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects; D006133:Growth Substances / Q000737:chemistry* / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D006133:Growth Substances; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor