Conserved patterns of microbial immune escape : pathogenic microbes of diverse origin target the human terminal complement inhibitor vitronectin via a single common motif

  • Pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. Here we show that different human pathogens including Gram-negative and Gram-positive bacteria, as well as the fungal pathogen Candida albicans, acquire the human terminal complement regulator vitronectin to their surface. By using truncated vitronectin fragments we found that all analyzed microbial pathogens (n = 13) bound human vitronectin via the same C-terminal heparin-binding domain (amino acids 352–374). This specific interaction leaves the terminal complement complex (TCC) regulatory region of vitronectin accessible, allowing inhibition of C5b-7 membrane insertion and C9 polymerization. Vitronectin complexed with the various microbes and corresponding proteins was thus functionally active and inhibited complement-mediated C5b-9 deposition. Taken together, diverse microbial pathogens expressing different structurally unrelated vitronectin-binding molecules interact with host vitronectin via the same conserved region to allow versatile control of the host innate immune response.

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Author:Teresia Hallström, Birendra Singh, Peter KraiczyGND, Sven Hammerschmidt, Christine SkerkaGND, Peter F. ZipfelORCiDGND, Kristian Riesbeck
Parent Title (English):PLoS One
Place of publication:Lawrence, Kan.
Document Type:Article
Date of Publication (online):2016/01/25
Date of first Publication:2016/01/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/02/01
Issue:(1): e0147709
Page Number:17
First Page:1
Last Page:17
Copyright: © 2016 Hallström et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 4.0