Division of Infection Medicine, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden;
Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
J Immunol. 2018 Aug 1;201(3):1007-1020. doi: 10.4049/jimmunol.1700602. Epub 2018 Jun 20.
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.
胶原 VI 是一种普遍存在的细胞外基质成分，在大多数结缔组织中形成广泛的微纤维网络。在这项研究中，我们首次描述了，据我们所知，胶原 VI 血管性血友病因子 A 样结构域在体内人类皮肤感染中表现出广谱抗革兰氏阳性和革兰氏阴性细菌的活性。VWA 结构域的计算机序列和结构分析表明，它们含有阳离子和两亲肽序列基序，这可能解释了胶原 VI 的抗菌性质。体外和体内研究表明，这些肽通过破坏细胞膜对 、 和 表现出显著的抗菌活性。我们的发现揭示了胶原六肽在天然宿主防御中的作用，并为基于肽的抗菌治疗提供了模板。
