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

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 ,, and 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.

High Throughput Identification of Antihypertensive Peptides from Fish Proteome Datasets

“…In addition, type IX collagen was required for the formation of vascular plexus [ 46 ], and the enzymatic fragments of salmon col7a1 isoform X5 also showed ACE inhibitory activity [ 37 ]. Previous studies also reported that collagen subunits contain multiple host defense peptides [ 47 ]. What is more, some collagen-derived peptides have antioxidant and anti-inflammatory capacities [ 48 ], and even can suppress allergic responses [ 49 ].…”

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

“…AMP discovery and development either involves identifying novel peptides from natural sources [e.g., organisms and tissue extracts Rodríguez-Decuadro et al, 2018;Yang D. et al, 2018;Yang L.L. et al, 2018), excised predicted antimicrobial sequences from larger proteins (Pane et al, 2016;Abdillahi et al, 2018;Pizzo et al, 2018)] or optimizing antibacterial activity by making synthetic variants (Bahar and Ren, 2013;Haney and Hancock, 2013;Zhao et al, 2013;Kim et al, 2014Kim et al, , 2016Wang et al, 2016;Kumar et al, 2017;Travkova et al, 2017;Akbari et al, 2018;Chen et al, 2018). The aim is generally to find a handful of peptide sequences with broad spectrum antimicrobial activity toward antibiotic resistant pathogens.…”

Proteomic Signature of Mesenchymal Stromal Cell‐Derived Small Extracellular Vesicles

“…Potentially collagen 1 and 6 can directly and indirectly contribute to the therapeutic potential of MSC‐EV. Collagen 6, for example, could have a direct antimicrobial effect through the activity of its von Willebrand factor type A‐like domains . Also, collagen 6, by influencing the ECM microenvironment, could skew macrophages to the regenerative M2 phenotype, or stimulate fibroblast polarization and migration, as observed in tendon repair, through NG2 binding .…”