Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD)

PLoS Pathog. 2013 Sep;9(9):e1003627. doi: 10.1371/journal.ppat.1003627. Epub 2013 Sep 12.


Rheumatoid arthritis and periodontitis are two prevalent chronic inflammatory diseases in humans and are associated with each other both clinically and epidemiologically. Recent findings suggest a causative link between periodontal infection and rheumatoid arthritis via bacteria-dependent induction of a pathogenic autoimmune response to citrullinated epitopes. Here we showed that infection with viable periodontal pathogen Porphyromonas gingivalis strain W83 exacerbated collagen-induced arthritis (CIA) in a mouse model, as manifested by earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction. The ability of P. gingivalis to augment CIA was dependent on the expression of a unique P. gingivalis peptidylarginine deiminase (PPAD), which converts arginine residues in proteins to citrulline. Infection with wild type P. gingivalis was responsible for significantly increased levels of autoantibodies to collagen type II and citrullinated epitopes as a PPAD-null mutant did not elicit similar host response. High level of citrullinated proteins was also detected at the site of infection with wild-type P. gingivalis. Together, these results suggest bacterial PAD as the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / immunology
  • Arthritis / microbiology*
  • Arthritis / pathology
  • Arthritis / physiopathology
  • Autoantibodies / analysis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacteroidaceae Infections / immunology
  • Bacteroidaceae Infections / microbiology*
  • Bacteroidaceae Infections / pathology
  • Bacteroidaceae Infections / physiopathology
  • Bone Resorption / etiology
  • Citrulline / metabolism
  • Disease Models, Animal*
  • Disease Progression
  • Gene Deletion
  • Hydrolases / genetics
  • Hydrolases / metabolism*
  • Joints / immunology
  • Joints / metabolism
  • Joints / microbiology
  • Joints / pathology
  • Male
  • Mice, Inbred DBA
  • Neutrophil Infiltration
  • Periodontitis / immunology
  • Periodontitis / metabolism
  • Periodontitis / microbiology*
  • Periodontitis / pathology
  • Porphyromonas gingivalis / enzymology*
  • Porphyromonas gingivalis / immunology
  • Porphyromonas gingivalis / isolation & purification
  • Prevotella intermedia / enzymology
  • Prevotella intermedia / immunology
  • Prevotella intermedia / isolation & purification
  • Protein Processing, Post-Translational
  • Protein-Arginine Deiminases
  • Severity of Illness Index


  • Autoantibodies
  • Bacterial Proteins
  • Citrulline
  • Hydrolases
  • Protein-Arginine Deiminases