title: Dermatan sulphate is released by proteinases of common pathogenic bacteria and inactivates antibacterial alpha-defensin.
abstract: Defensins represent an evolutionarily conserved group of small peptides with potent antibacterial activities. We report here that extracellular proteinases secreted by the human pathogens Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus pyogenes release dermatan sulphate by degrading dermatan sulphate-containing proteoglycans, such as decorin. Dermatan sulphate was found to bind to neutrophil-derived alpha-defensin, and this binding completely neutralized its bactericidal activity. During infection, proteoglycan degradation and release of dermatan sulphate may therefore represent a previously unknown virulence mechanism, which could serve as a target for novel antibacterial strategies.
authors.affiliation: Section for Molecular Pathogenesis, Department of Cell and Molecular Biology, Biomedical Center, B14, Lund University, Tornavägen 10, Se-22184, Lund, Sweden. artur.schmidtchen@derm.lu.se
authors.forename: A
authors.initials: A
authors.lastname: Schmidtchen
authors.forename: I M
authors.initials: IM
authors.lastname: Frick
authors.forename: L
authors.initials: L
authors.lastname: Björck
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism; D001424:Bacterial Infections / Q000382:microbiology; D002478:Cells, Cultured; D058575:Decorin; D003871:Dermatan Sulfate / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D013293:Enterococcus faecalis / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D011509:Proteoglycans / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D023084:alpha-Defensins; D003871:Dermatan Sulfate; D010450:Endopeptidases