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J Immunol. 2018 Aug 1;201(3):1007-1020. doi: 10.4049/jimmunol.1700602. Epub 2018 Jun 20.

Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity.

Author information

1
Division of Infection Medicine, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden; suado.abdillahi@gmail.com.
2
Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
3
Division of Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden.
4
Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden.
5
Division of Infection Medicine, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden.
6
Saromics Biostructures AB, 223 63 Lund, Sweden.
7
Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden.
8
Copenhagen Wound Healing Center, Bispebjerg Hospital, Department of Biomedical Sciences, University of Copenhagen, 2400 Copenhagen, Denmark and.
9
Colzyx AB, 223 81 Lund, Sweden.

Abstract

Collagen VI is a ubiquitous extracellular matrix component that forms extensive microfibrillar networks in most connective tissues. In this study, we describe for the first time, to our knowledge, that the collagen VI von Willebrand factor type A-like domains exhibit a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria in human skin infections in vivo. In silico sequence and structural analysis of VWA domains revealed that they contain cationic and amphipathic peptide sequence motifs, which might explain the antimicrobial nature of collagen VI. In vitro and in vivo studies show that these peptides exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa through membrane disruption. Our findings shed new light on the role of collagen VI-derived peptides in innate host defense and provide templates for development of peptide-based antibacterial therapies.

PMID:
29925677
DOI:
10.4049/jimmunol.1700602
[Indexed for MEDLINE]
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