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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.

Hallström, Teresia; Singh, Birendra LU ; Kraiczy, Peter; Hammerschmidt, Sven; Skerka, Christine; Zipfel, Peter F and Riesbeck, Kristian LU (2016) In PLoS ONE 11(1).
Abstract
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... (More)
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. (Less)
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published
subject
in
PLoS ONE
volume
11
issue
1
publisher
Public Library of Science
external identifiers
  • pmid:26808444
  • scopus:84959232606
  • wos:000369527800189
ISSN
1932-6203
DOI
10.1371/journal.pone.0147709
language
English
LU publication?
yes
id
1359dea9-dba2-4da8-9158-bdf6e74e41f7 (old id 8573737)
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http://www.ncbi.nlm.nih.gov/pubmed/26808444?dopt=Abstract
date added to LUP
2016-02-04 21:19:07
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2017-09-17 08:36:39
@article{1359dea9-dba2-4da8-9158-bdf6e74e41f7,
  abstract     = {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.},
  articleno    = {e0147709},
  author       = {Hallström, Teresia and Singh, Birendra and Kraiczy, Peter and Hammerschmidt, Sven and Skerka, Christine and Zipfel, Peter F and Riesbeck, Kristian},
  issn         = {1932-6203},
  language     = {eng},
  number       = {1},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Conserved Patterns of Microbial Immune Escape: Pathogenic Microbes of Diverse Origin Target the Human Terminal Complement Inhibitor Vitronectin via a Single Common Motif.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0147709},
  volume       = {11},
  year         = {2016},
}