Identification of a new genetic variant (G231N, E232T, N235D) of peptidylarginine deiminase from P. gingivalis in advanced periodontitis.

Autor:	Bereta GP; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland., Strzelec K; Department of Molecular Biology and Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland., Łazarz-Bartyzel K; Department of Periodontology, Preventive Dentistry and Oral Pathology, Faculty of Medicine, Medical College, Jagiellonian University, Krakow, Poland., Dziedzic-Kowalska A; Department of Molecular Biology and Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland., Nowakowska Z; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Krutyhołowa A; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Bielecka E; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland., Kantyka T; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland., Grabiec AM; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Kaczmarzyk T; Department of Oral Surgery, Medical College, Jagiellonian University, Krakow, Poland., Chomyszyn-Gajewska M; Department of Periodontology, Preventive Dentistry and Oral Pathology, Faculty of Medicine, Medical College, Jagiellonian University, Krakow, Poland., Potempa J; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY, United States., Gawron K; Department of Molecular Biology and Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Mar 21; Vol. 15, pp. 1355357. Date of Electronic Publication: 2024 Mar 21 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1355357
Abstrakt:	Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic diseases, including rheumatoid arthritis (RA). Porphyromonas gingivalis , one of the bacterial species implicated in CP as a keystone pathogen produces peptidyl arginine deiminase (PPAD) that citrullinates C-terminal arginine residues in proteins and peptides. Autoimmunity to citrullinated epitopes is crucial in RA, hence PPAD activity is considered a possible mechanistic link between CP and RA. Here we determined the PPAD enzymatic activity produced by clinical isolates of P. gingivalis , sequenced the ppad gene, and correlated the results with clinical determinants of CP in patients from whom the bacteria were isolated. The analysis revealed variations in PPAD activity and genetic diversity of the ppad gene in clinical P. gingivalis isolates. Interestingly, the severity of CP was correlated with a higher level of PPAD activity that was associated with the presence of a triple mutation (G231N, E232T, N235D) in PPAD in comparison to W83 and ATCC 33277 type strains. The relation between mutations and enhanced activity was verified by directed mutagenesis which showed that all three amino acid residue substitutions must be introduced into PPAD expressed by the type strains to obtain the super-active enzyme. Cumulatively, these results may lead to the development of novel prognostic tools to assess the progress of CP in the context of associated RA by analyzing the ppad genotype in CP patients infected with P. gingivalis . Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Bereta, Strzelec, Łazarz-Bartyzel, Dziedzic-Kowalska, Nowakowska, Krutyhołowa, Bielecka, Kantyka, Grabiec, Kaczmarzyk, Chomyszyn-Gajewska, Potempa and Gawron.)
Databáze:	MEDLINE
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