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

2024
journal article
article
dc.abstract.enChronic 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.
dc.affiliationPion Prorektora ds. badań naukowych : Małopolskie Centrum Biotechnologii
dc.affiliationWydział Lekarski : Instytut Stomatologii
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologii
dc.cm.id115078
dc.cm.idOmegaUJCM73c428a9699b4495aa7515195e7aa785
dc.contributor.authorBereta, Grzegorz - 202762
dc.contributor.authorStrzelec, Karolina
dc.contributor.authorŁazarz-Bartyzel, Katarzyna - 173934
dc.contributor.authorDziedzic-Kowalska, Agata
dc.contributor.authorNowakowska, Zuzanna - 148651
dc.contributor.authorKrutyhołowa, Anna
dc.contributor.authorBielecka, Ewa - 115316
dc.contributor.authorKantyka, Tomasz - 173997
dc.contributor.authorGrabiec, Aleksander - 104028
dc.contributor.authorKaczmarzyk, Tomasz - 129950
dc.contributor.authorChomyszyn-Gajewska, Maria - 129012
dc.contributor.authorPotempa, Jan - 131531
dc.contributor.authorGawron, Katarzyna - 200071
dc.date.accession2024-05-22pl
dc.date.accessioned2024-05-09T07:47:29Z
dc.date.available2024-05-09T07:47:29Z
dc.date.issued2024
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.additionalBibliogr. Grzegorz Bereta podpisany: Grzegorz P. Bereta. Aleksander Grabiec podpisany: Aleksander M. Grabiec
dc.description.versionostateczna wersja wydawcy
dc.description.volume15
dc.identifier.articleid1355357
dc.identifier.doi10.3389/fimmu.2024.1355357
dc.identifier.eissn1664-3224
dc.identifier.issn1664-3224pl
dc.identifier.urihttps://ruj.uj.edu.pl/handle/item/339252
dc.identifier.weblinkhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1355357/fullpl
dc.languageeng
dc.language.containereng
dc.pbn.affiliationDziedzina nauk medycznych i nauk o zdrowiu : nauki medyczne
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.typeOtwarte czasopismo
dc.subject.enchronic periodontitis
dc.subject.enP. gingivalis
dc.subject.envirulence
dc.subject.enpeptidylarginine deiminase
dc.subject.enpolymorphic variant(s)
dc.subject.engenetic variability
dc.subject.endisease prognosis
dc.subtypeArticle
dc.titleIdentification of a new genetic variant (G231N, E232T, N235D) of peptidylarginine deiminase from P. gingivalis in advanced periodontitis
dc.title.journalFrontiers in Immunology
dc.typeJournalArticle
dspace.entity.typePublication
dc.abstract.en
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.
dc.affiliation
Pion Prorektora ds. badań naukowych : Małopolskie Centrum Biotechnologii
dc.affiliation
Wydział Lekarski : Instytut Stomatologii
dc.affiliation
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologii
dc.cm.id
115078
dc.cm.idOmega
UJCM73c428a9699b4495aa7515195e7aa785
dc.contributor.author
Bereta, Grzegorz - 202762
dc.contributor.author
Strzelec, Karolina
dc.contributor.author
Łazarz-Bartyzel, Katarzyna - 173934
dc.contributor.author
Dziedzic-Kowalska, Agata
dc.contributor.author
Nowakowska, Zuzanna - 148651
dc.contributor.author
Krutyhołowa, Anna
dc.contributor.author
Bielecka, Ewa - 115316
dc.contributor.author
Kantyka, Tomasz - 173997
dc.contributor.author
Grabiec, Aleksander - 104028
dc.contributor.author
Kaczmarzyk, Tomasz - 129950
dc.contributor.author
Chomyszyn-Gajewska, Maria - 129012
dc.contributor.author
Potempa, Jan - 131531
dc.contributor.author
Gawron, Katarzyna - 200071
dc.date.accessionpl
2024-05-22
dc.date.accessioned
2024-05-09T07:47:29Z
dc.date.available
2024-05-09T07:47:29Z
dc.date.issued
2024
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.additional
Bibliogr. Grzegorz Bereta podpisany: Grzegorz P. Bereta. Aleksander Grabiec podpisany: Aleksander M. Grabiec
dc.description.version
ostateczna wersja wydawcy
dc.description.volume
15
dc.identifier.articleid
1355357
dc.identifier.doi
10.3389/fimmu.2024.1355357
dc.identifier.eissn
1664-3224
dc.identifier.issnpl
1664-3224
dc.identifier.uri
https://ruj.uj.edu.pl/handle/item/339252
dc.identifier.weblinkpl
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1355357/full
dc.language
eng
dc.language.container
eng
dc.pbn.affiliation
Dziedzina nauk medycznych i nauk o zdrowiu : nauki medyczne
dc.rights
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
Otwarte czasopismo
dc.subject.en
chronic periodontitis
dc.subject.en
P. gingivalis
dc.subject.en
virulence
dc.subject.en
peptidylarginine deiminase
dc.subject.en
polymorphic variant(s)
dc.subject.en
genetic variability
dc.subject.en
disease prognosis
dc.subtype
Article
dc.title
Identification of a new genetic variant (G231N, E232T, N235D) of peptidylarginine deiminase from P. gingivalis in advanced periodontitis
dc.title.journal
Frontiers in Immunology
dc.type
JournalArticle
dspace.entity.type
Publication

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