TY - JOUR
T1 - Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis
AU - Stobernack, Tim
AU - Glasner, Corinna
AU - Junker, Sabryna
AU - Gabarrini, Giorgio
AU - de Smit, Menke
AU - de Jong, Anne
AU - Otto, Andreas
AU - Becher, Doerte
AU - van Winkelhoff, Arie Jan
AU - van Dijl, Jan Maarten
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Porphyromonas gingivalis
KW - protein sorting
KW - exoproteome
KW - citrullination
KW - peptidylarginine deiminase
KW - SUBCELLULAR-LOCALIZATION PREDICTION
KW - GRAM-NEGATIVE BACTERIA
KW - RHEUMATOID-ARTHRITIS
KW - PEPTIDYLARGININE DEIMINASE
KW - STAPHYLOCOCCUS-AUREUS
KW - BACILLUS-SUBTILIS
KW - SIGNAL PEPTIDES
KW - BACTEROIDES-GINGIVALIS
KW - OUTER-MEMBRANE
KW - VIRULENCE
U2 - 10.1021/acs.jproteome.6b00634
DO - 10.1021/acs.jproteome.6b00634
M3 - Article
C2 - 27712078
SN - 1535-3893
VL - 15
SP - 4532
EP - 4543
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 12
ER -