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Conserved Patterns of Microbial Immune Escape: Pathogenic Microbes of Diverse Origin Target the Human Terminal Complement Inhibitor Vitronectin via a Single Common Motif.

Författare

  • Teresia Hallström
  • Birendra Singh
  • Peter Kraiczy
  • Sven Hammerschmidt
  • Christine Skerka
  • Peter F Zipfel
  • Kristian Riesbeck

Summary, in English

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.

Publiceringsår

2016

Språk

Engelska

Publikation/Tidskrift/Serie

PLoS ONE

Volym

11

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Public Library of Science (PLoS)

Ämne

  • Microbiology in the medical area

Status

Published

Forskningsgrupp

  • Clinical Microbiology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1932-6203