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Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape

Peptidylarginine deiminase (PPAD) is a virulence factor unique to pathogenic Porphyromonas species, especially P. gingivalis. Mechanistically, PPAD activity, in conjunction with Arg-specific gingipains, generates protein fragments with citrullinated C-termini. Such polypeptides are potential de novo...

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Autores principales: Aliko, Ardita, Kamińska, Marta, Bergum, Brith, Gawron, Katarzyna, Benedyk, Małgorzata, Lamont, Richard J., Malicki, Stanisław, Delaleu, Nicolas, Potempa, Jan, Mydel, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147916/
https://www.ncbi.nlm.nih.gov/pubmed/30237466
http://dx.doi.org/10.1038/s41598-018-32603-y
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author Aliko, Ardita
Kamińska, Marta
Bergum, Brith
Gawron, Katarzyna
Benedyk, Małgorzata
Lamont, Richard J.
Malicki, Stanisław
Delaleu, Nicolas
Potempa, Jan
Mydel, Piotr
author_facet Aliko, Ardita
Kamińska, Marta
Bergum, Brith
Gawron, Katarzyna
Benedyk, Małgorzata
Lamont, Richard J.
Malicki, Stanisław
Delaleu, Nicolas
Potempa, Jan
Mydel, Piotr
author_sort Aliko, Ardita
collection PubMed
description Peptidylarginine deiminase (PPAD) is a virulence factor unique to pathogenic Porphyromonas species, especially P. gingivalis. Mechanistically, PPAD activity, in conjunction with Arg-specific gingipains, generates protein fragments with citrullinated C-termini. Such polypeptides are potential de novo epitopes that are key drivers of rheumatoid arthritis. This process could underlie the observed clinical association between rheumatoid arthritis and periodontitis. However, the role of PPAD in host colonization by P. gingivalis and, subsequently, in triggering periodontitis is not known. Therefore, the aim of the current study was to delineate the role of PPAD in bacterial biofilm formation, and to define whether adherence to, invasion of, and host responses to bacteria of gingival keratinocytes depend on PPAD activity. We studied these aspects using PPAD-competent and PPAD-incompetent strains of P. gingivalis, and demonstrated that neither biofilm formation nor its composition was affected by PPAD activity. Similarly, flow cytometry revealed that PPAD did not impact the ability of P. gingivalis to adhere to and, subsequently, invade keratinocytes. Network analyses of gene expression patterns, however, revealed a group of host genes that were sensitive to PPAD activity (CXCL8, IL36G, CCL20, and IL1B). These genes can be categorized as potent immune modulators belonging to the interleukin 1 system, or chemoattractants of lymphocytes and neutrophils. Thus, we conclude that PPAD, although it is a potent modulator of the immune response, does not affect bacterial biofilm formation or the ability of P. gingivalis to adhere to and invade gingival epithelial cells.
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spelling pubmed-61479162019-02-12 Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape Aliko, Ardita Kamińska, Marta Bergum, Brith Gawron, Katarzyna Benedyk, Małgorzata Lamont, Richard J. Malicki, Stanisław Delaleu, Nicolas Potempa, Jan Mydel, Piotr Sci Rep Article Peptidylarginine deiminase (PPAD) is a virulence factor unique to pathogenic Porphyromonas species, especially P. gingivalis. Mechanistically, PPAD activity, in conjunction with Arg-specific gingipains, generates protein fragments with citrullinated C-termini. Such polypeptides are potential de novo epitopes that are key drivers of rheumatoid arthritis. This process could underlie the observed clinical association between rheumatoid arthritis and periodontitis. However, the role of PPAD in host colonization by P. gingivalis and, subsequently, in triggering periodontitis is not known. Therefore, the aim of the current study was to delineate the role of PPAD in bacterial biofilm formation, and to define whether adherence to, invasion of, and host responses to bacteria of gingival keratinocytes depend on PPAD activity. We studied these aspects using PPAD-competent and PPAD-incompetent strains of P. gingivalis, and demonstrated that neither biofilm formation nor its composition was affected by PPAD activity. Similarly, flow cytometry revealed that PPAD did not impact the ability of P. gingivalis to adhere to and, subsequently, invade keratinocytes. Network analyses of gene expression patterns, however, revealed a group of host genes that were sensitive to PPAD activity (CXCL8, IL36G, CCL20, and IL1B). These genes can be categorized as potent immune modulators belonging to the interleukin 1 system, or chemoattractants of lymphocytes and neutrophils. Thus, we conclude that PPAD, although it is a potent modulator of the immune response, does not affect bacterial biofilm formation or the ability of P. gingivalis to adhere to and invade gingival epithelial cells. Nature Publishing Group UK 2018-09-20 /pmc/articles/PMC6147916/ /pubmed/30237466 http://dx.doi.org/10.1038/s41598-018-32603-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Aliko, Ardita
Kamińska, Marta
Bergum, Brith
Gawron, Katarzyna
Benedyk, Małgorzata
Lamont, Richard J.
Malicki, Stanisław
Delaleu, Nicolas
Potempa, Jan
Mydel, Piotr
Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
title Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
title_full Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
title_fullStr Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
title_full_unstemmed Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
title_short Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional Landscape
title_sort impact of porphyromonas gingivalis peptidylarginine deiminase on bacterial biofilm formation, epithelial cell invasion, and epithelial cell transcriptional landscape
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147916/
https://www.ncbi.nlm.nih.gov/pubmed/30237466
http://dx.doi.org/10.1038/s41598-018-32603-y
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