Proteolytic inactivation of LL-37 by karilysin, a novel virulence mechanism of Tannerella forsythia.
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.
Koziel
Joanna
J
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. joanna.koziel @ uj.edu.pl
Karim
Aabdulkarim Y
AY
Przybyszewska
Kornelia
K
Ksiazek
Miroslaw
M
Rapala-Kozik
Maria
M
Nguyen
Ky-Anh
KA
Potempa
Jan
J
D000900:Anti-Bacterial Agents / Q000276:immunology / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001439:Bacteroides / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D001442:Bacteroides Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D018450:Disease Progression; D006801:Humans; D057131:Immune Evasion; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014774:Virulence; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D053505:Matrix Metalloproteinases, Secreted; D054804:Cathelicidins