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Binding of complement inhibitor C4b-binding protein contributes to serum resistance of Porphyromonas gingivalis.

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Author

Summary, in English

The periodontal pathogen Porphyromonas gingivalis is highly resistant to the bactericidal activity of human complement, which is present in the gingival crevicular fluid at 70% of serum concentration. All thirteen clinical and laboratory P. gingivalis strains tested were able to capture the human complement inhibitor C4b-binding protein (C4BP), which may contribute to their serum resistance. Accordingly, in serum deficient of C4BP, it was found that significantly more terminal complement component C9 was deposited on P. gingivalis. Moreover, using purified proteins and various isogenic mutants, we found that the cysteine protease high molecular weight arginine-gingipain A (HRgpA) is a crucial C4BP ligand on the bacterial surface. Binding of C4BP to P. gingivalis appears to be localized to two binding sites: on the complement control protein 1 domain and complement control protein 6 and 7 domains of the alpha-chains. Furthermore, the bacterial binding of C4BP was found to increase with time of culture and a particularly strong binding was observed for large aggregates of bacteria that formed during culture on solid blood agar medium. Taken together, gingipains appear to be a very significant virulence factor not only destroying complement due to proteolytic degradation as we have shown previously, but was also inhibiting complement activation due to their ability to bind the complement inhibitor C4BP.

Publishing year

2008

Language

English

Pages

5537-5544

Publication/Series

Journal of immunology

Volume

181

Issue

8

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Immunology in the medical area

Keywords

  • Porphyromonas gingivalis: enzymology
  • Porphyromonas gingivalis: immunology
  • Porphyromonas gingivalis: pathogenicity
  • Protein Binding: genetics
  • Protein Binding: immunology
  • Protein Structure
  • Secondary: genetics
  • Tertiary: genetics
  • Virulence Factors: genetics
  • Virulence Factors: immunology
  • Virulence Factors: metabolism
  • Cysteine Endopeptidases: metabolism
  • Cysteine Endopeptidases: immunology
  • Cysteine Endopeptidases: genetics
  • Complement C9: metabolism
  • Complement C9: immunology
  • Complement C9: genetics
  • Complement C4b-Binding Protein: metabolism
  • Complement C4b-Binding Protein: immunology
  • Complement C4b-Binding Protein: genetics
  • Complement Activation: immunology
  • Complement Activation: genetics
  • Blood Bactericidal Activity: immunology
  • Blood Bactericidal Activity: genetics
  • Bacteroidaceae Infections: immunology
  • Bacteroidaceae Infections: genetics
  • Bacteroidaceae Infections: enzymology
  • Bacterial: metabolism
  • Adhesins
  • Bacterial: genetics
  • Bacterial: immunology

Status

Published

Research group

  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1550-6606