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

Potempa, Michal; Potempa, Michal LU ; Okroj, Marcin LU ; Popadiak, Katarzyna LU ; Eick, Sigrun; Nguyen, Ky-Anh; Riesbeck, Kristian LU and Blom, Anna LU (2008) In Journal of immunology (Baltimore, Md. : 1950) 181(8). p.5537-5544
Abstract
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... (More)
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. (Less)
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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
in
Journal of immunology (Baltimore, Md. : 1950)
volume
181
issue
8
pages
5537 - 5544
publisher
American Association of Immunologists
external identifiers
  • WOS:000260025300046
  • PMID:18832711
  • Scopus:54049101495
ISSN
1550-6606
language
English
LU publication?
yes
id
a14e6f0a-908d-4545-be76-0d35da14af04 (old id 1262589)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18832711?dopt=Abstract
date added to LUP
2008-11-05 14:34:58
date last changed
2016-11-01 10:16:42
@misc{a14e6f0a-908d-4545-be76-0d35da14af04,
  abstract     = {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.},
  author       = {Potempa, Michal and Potempa, Michal and Okroj, Marcin and Popadiak, Katarzyna and Eick, Sigrun and Nguyen, Ky-Anh and Riesbeck, Kristian and Blom, Anna},
  issn         = {1550-6606},
  keyword      = {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},
  language     = {eng},
  number       = {8},
  pages        = {5537--5544},
  publisher    = {ARRAY(0xa099670)},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Binding of complement inhibitor C4b-binding protein contributes to serum resistance of Porphyromonas gingivalis.},
  volume       = {181},
  year         = {2008},
}