Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis

Tim Stobernack, Corinna Glasner, Sabryna Junker, Giorgio Gabarrini, Menke de Smit, Anne de Jong, Andreas Otto, Doerte Becher, Arie Jan van Winkelhoff, Jan Maarten van Dijl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)

Abstract

Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is a post translational modification of arginine residues, leading to a change in structure and function of the respective protein. This modification, which is catalyzed by peptidylarginine deiminases (PADs), plays a role in several physiological processes in the human body. Interestingly, P. gingivalis secretes a citrullinating enzyme, known as P. gingivalis PAD (PPAD), which targets bacterial and human proteins. Because the extent of P. gingivalis protein citrullination by PPAD was not yet known, the present study was aimed at identifying the extracellular proteome and citrullinome of P. gingivalis. To this end, extracellulai proteins of two reference strains, two PPAD-deficient mutants, and three clinical isolates of P. gingivalis were analyzed by mass spectrometry. The results uncovered substantial heterogeneity in the extracellular proteome and citrullinome of P. gingivalis, especially in relation to the extracellular detection of typical cytoplasmic proteins. In contrast, the major virulence factors of P. gingivalis were identified in all investigated isolates, although their citrullination was shown to vary. This may be related to post-translational processing of the PPAD enzyme. Altogether, our findings focus attention on the possible roles of 6 to 25 potentially citrullinated proteins, especially the gingipain RgpA, in periodontitis and rheumatoid arthritis.

Original languageEnglish
Pages (from-to)4532-4543
Number of pages12
JournalJournal of Proteome Research
Volume15
Issue number12
DOIs
Publication statusPublished - Dec-2016

Keywords

  • Porphyromonas gingivalis
  • protein sorting
  • exoproteome
  • citrullination
  • peptidylarginine deiminase
  • SUBCELLULAR-LOCALIZATION PREDICTION
  • GRAM-NEGATIVE BACTERIA
  • RHEUMATOID-ARTHRITIS
  • PEPTIDYLARGININE DEIMINASE
  • STAPHYLOCOCCUS-AUREUS
  • BACILLUS-SUBTILIS
  • SIGNAL PEPTIDES
  • BACTEROIDES-GINGIVALIS
  • OUTER-MEMBRANE
  • VIRULENCE

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