title: Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis.
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, extracellular 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.
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Stobernack
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.
authors.forename: Corinna
authors.initials: C
authors.lastname: Glasner
authors.affiliation: Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald , Greifswald 17489, Germany.
authors.forename: Sabryna
authors.initials: S
authors.lastname: Junker
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.|Center for Dentistry and Oral Hygiene, Department of Periodontology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gabarrini
authors.affiliation: Center for Dentistry and Oral Hygiene, Department of Periodontology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.
authors.forename: Menke
authors.initials: M
authors.lastname: de Smit
authors.affiliation: Department of Molecular Genetics, University of Groningen , Groningen 9700 AB, The Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: de Jong
authors.affiliation: Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald , Greifswald 17489, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Otto
authors.affiliation: Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald , Greifswald 17489, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Becher
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.|Center for Dentistry and Oral Hygiene, Department of Periodontology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.
authors.forename: Arie Jan
authors.initials: AJ
authors.lastname: van Winkelhoff
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen , Groningen 9700 RB, The Netherlands.
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: van Dijl
mesh_terms: D001172:Arthritis, Rheumatoid / Q000382:microbiology*; D001426:Bacterial Proteins / Q000378:metabolism; D016866:Bacteroidaceae Infections; D002956:Citrulline / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D010518:Periodontitis / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000737:chemistry* / Q000472:pathogenicity; D011499:Protein Processing, Post-Translational; D000076342:Protein-Arginine Deiminases; D020543:Proteome / Q000032:analysis*; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D037521:Virulence Factors; D002956:Citrulline; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases
keywords: Porphyromonas gingivalis; citrullination; exoproteome; peptidylarginine deiminase; protein sorting