Porphyromonas gingivalis, the beast with two heads: A bacterial role in the etiology of rheumatoid arthritis

Gabarrini, G., 2018, [Groningen]: University of Groningen. 384 p.

Research output: ThesisThesis fully internal (DIV)

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  • Title and contents

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  • Chapter 1

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  • Chapter 2

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  • Chapter 3

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  • Chapter 4

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  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Chapter 8

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  • Chapter 9

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  • Chapter 10

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  • Chapter 11

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  • Appendices

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  • Complete thesis

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  • Propositions

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  • Giorgio Gabarrini
Porphyromonas gingivalis is a renowned oral pathogen involved in periodontitis, one of the most common inflammatory diseases worldwide. The recent discovery of its citrullinating enzyme, the Porphyromonas peptidylarginine deiminase (PPAD), has focused attention on its potential involvement in the autoimmune disease rheumatoid arthritis (RA), as autoantibodies against citrullinated proteins are a hallmark of RA. In the present PhD thesis, possible etiological mechanisms implicating the PPAD enzyme and members of the gut and oral microbiome in the intricate processes leading to the development of RA are discussed. Additionally, the cell architecture, transport systems and protein localization in P. gingivalis have been dissected in a multi-strain analysis with the potential side benefit of identifying proteins interacting with PPAD. Moreover, the conservation of PPAD was analyzed at the gene and protein levels in a panel of 100 clinical P. gingivalis isolates, showing that this enzyme is a universal fixture of P. gingivalis. Despite its highly conserved nucleotide sequence, the PPAD protein can be aberrantly sorted by a subset of clinical isolates due to a point mutation in its Ig-like fold domain. This mutation leads to marginal attachment of PPAD to the outer membrane of the bacterium, an association facilitated by a special form of lipopolysaccharide known as A-LPS. Lastly, it was shown that the level of conservation of PPAD crosses the species barrier, as orthologues of this enzyme were found in different Porphyromonas species isolated from animals. Altogether, the present studies highlight possible roles of P. gingivalis in the onset of RA.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • van Winkelhoff, Arie Jan, Supervisor
  • Dijl, van, Jan Maarten, Supervisor
  • Quax, W. J., Assessment committee
  • Robinson, Colin, Assessment committee, External person
  • Bitter, Wilbert, Assessment committee, External person
Award date12-Dec-2018
Place of Publication[Groningen]
Print ISBNs978-94-034-1275-7
Electronic ISBNs978-94-034-1274-0
Publication statusPublished - 2018

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