Proteolytic inactivation of LL-37 by karilysin, a novel virulence mechanism of Tannerella forsythia

J Innate Immun. 2010;2(3):288-93. doi: 10.1159/000281881. Epub 2010 Feb 4.

Abstract

Tannerella forsythia is a gram-negative bacterium strongly associated with the development and/or progression of periodontal disease. Here, we have shown that a newly characterized matrix metalloprotease-like enzyme, referred to as karilysin, efficiently cleaved the antimicrobial peptide LL-37, significantly reducing its bactericidal activity. This may contribute to the resistance of T. forsythia to the antibacterial activity of LL-37, since their vitality was found not to be affected by LL-37 at concentrations up to 2.2 muM. Furthermore, proteolysis of LL-37 by karilysin not only abolished its ability to bind lipopolysaccharide (LPS) to quench endotoxin-induced proinflammatory activity, but LL-37 cleavage also caused the release of active endotoxin from the LPS/LL-37 complex. Proteolytic inactivation of LL-37 bactericidal activity by karilysin may protect LL-37-sensitive species in the subgingival plaque and maintain the local inflammatory reaction driven by LPS from gram-negative bacteria. Consequently, the karilysin protease may directly contribute to periodontal tissue damage and the development and/or progression of chronic periodontitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / immunology
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / metabolism*
  • Bacteroides / growth & development
  • Bacteroides / immunology*
  • Bacteroides / pathogenicity
  • Bacteroides Infections / immunology*
  • Bacteroides Infections / microbiology
  • Bacteroides Infections / physiopathology
  • Cathelicidins
  • Cells, Cultured
  • Colony Count, Microbial
  • Disease Progression
  • Humans
  • Immune Evasion
  • Lipopolysaccharides / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Macrophages / pathology
  • Matrix Metalloproteinases, Secreted / genetics
  • Matrix Metalloproteinases, Secreted / immunology
  • Matrix Metalloproteinases, Secreted / metabolism*
  • Periodontitis / immunology*
  • Periodontitis / microbiology
  • Periodontitis / physiopathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Virulence

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinases, Secreted
  • Cathelicidins