Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses

Nat Commun. 2016 May 16;7:11567. doi: 10.1038/ncomms11567.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived peptide FYT21, which inhibits pro-inflammatory responses to several pathogen-associated molecular patterns in vitro and in vivo by preventing toll-like receptor dimerization and subsequent activation of down-stream signalling pathways. Thus, P. aeruginosa 'hijacks' an endogenous anti-inflammatory peptide-based mechanism, thereby enabling modulation and circumvention of host responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Cell Membrane / metabolism
  • Cytokines / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Inflammation / pathology*
  • Leukocytes / metabolism
  • Leukocytes / ultrastructure
  • Lipopolysaccharides / metabolism
  • Metalloendopeptidases / metabolism*
  • Mice
  • Microbial Viability
  • NF-kappa B / metabolism
  • Peptides / isolation & purification
  • Peptides / metabolism*
  • Protein Binding
  • Thrombin / metabolism*
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor AP-1 / metabolism

Substances

  • Bacterial Proteins
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Peptides
  • Toll-Like Receptor 4
  • Transcription Factor AP-1
  • Thrombin
  • Metalloendopeptidases
  • pseudolysin, Pseudomonas aeruginosa