The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis

Gabarrini, Giorgio; Smit, Menke de; Westra, Johanna; Brouwer, Elisabeth; Vissink, Arjan; Zhou, Kai; Rossen, John W. A.; Stobernack, Tim; Dijl, Jan Maarten van; Winkelhoff, A.J. van

doi:10.1038/srep13936

Cited by 54 publications

(69 citation statements)

References 22 publications

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“…This same effect is observed when comparing the cultures the bacterial strains, where these two bacteria were the only ones that showed an increase in ammonium generation. We would primarily support the hypothesis that the increase in ammonium content in our enzymatic assay is a consequence of the action of PAD proteins, an event clearly demonstrated for P. gingivalis (Gabarrini et al, , Montgomery et al, ); however, it remains to be evaluated in the case of T. forsythia . In any case, the results of this study suggest that the high prevalence of T. forsythia significantly alters the oral microenvironment and that this change seems to be related to the increased clinical activity in patients with RA.…”

Section: Discussionsupporting

confidence: 79%

Salivary ammonia levels andTannerella forsythiaare associated with rheumatoid arthritis: A cross sectional study

Martínez-Rivera

Xibillé-Friedmann

González-Christen

et al. 2017

Clinical & Exp Dental Res

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The aim of this paper is to evaluate the relationship of salivary ammonium levels and the presence of bacteria with rheumatoid arthritis (RA) clinical disease activity in a cross‐sectional study of Mexican patients. From a periodontal and disease activity standpoint, 132 consecutive RA patients fulfilling clinical criteria were evaluated. Ammonia levels (including peptidyl arginine deiminase activity) were evaluated by colorimetric assay and the presence of Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia was evaluated by polymerase chain reaction (PCR) technique. After a multivariate analysis, adjusting for clinical and serological parameters, a significant association was only observed between severe periodontitis and probing depth with high RA disease activity. Additionally, in contrast to P. gingivalis, the presence of T. forsythia was significantly associated with high disease RA activity even after multivariable adjustment analysis. There was also a significant increase in ammonium levels in the high RA activity group and a significant correlation between salivary ammonia and RA disease activity but not with autoantibody titers. Similarly, we observed a significant increase in the ammonium levels derived from the cultures of P. gingivalis and T. forsythia, with respect to P. intermedia and S. gordonii cultures, or even healthy donors. These results suggest that RA activity is associated with severe periodontitis, high salivary ammonium levels and the presence of T. forsythia.

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Section: Discussionsupporting

confidence: 79%

Salivary ammonia levels andTannerella forsythiaare associated with rheumatoid arthritis: A cross sectional study

Martínez-Rivera

Xibillé-Friedmann

González-Christen

et al. 2017

Clinical & Exp Dental Res

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“…Conversely, abnormal citrullination can lead to severe human diseases. Epidemiologically, there seems to be a correlation between citrullination caused by P. gingivalis and PD [69,70] and between P. gingivalis and RA [14,71–73]. There is also an association between AS and RA [74].…”

Section: Discussionmentioning

confidence: 99%

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

Olsen

Singhrao

Potempa

2018

Journal of Oral Microbiology

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Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer’s disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. Porphyromonas gingivalis is unique in its ability to secrete the P. gingivalis-derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of P. gingivalis and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases such as RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore, PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.

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“…It is the first and only bacterial peptidylarginine deiminase (PAD) identified, and, moreover, its presence is limited to a single species: P. gingivalis (McGraw et al, 1999; Gabarrini et al, 2015). …”

Section: Protein Effectors In P Gingivalismentioning

confidence: 99%

The Type IX Secretion System (T9SS): Highlights and Recent Insights into Its Structure and Function

Łasica

Książek

Madej

et al. 2017

Front. Cell. Infect. Microbiol.

243

262

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Protein secretion systems are vital for prokaryotic life, as they enable bacteria to acquire nutrients, communicate with other species, defend against biological and chemical agents, and facilitate disease through the delivery of virulence factors. In this review, we will focus on the recently discovered type IX secretion system (T9SS), a complex translocon found only in some species of the Bacteroidetes phylum. T9SS plays two roles, depending on the lifestyle of the bacteria. It provides either a means of movement (called gliding motility) for peace-loving environmental bacteria or a weapon for pathogens. The best-studied members of these two groups are Flavobacterium johnsoniae, a commensal microorganism often found in water and soil, and Porphyromonas gingivalis, a human oral pathogen that is a major causative agent of periodontitis. In P. gingivalis and some other periodontopathogens, T9SS translocates proteins, especially virulence factors, across the outer membrane (OM). Proteins destined for secretion bear a conserved C-terminal domain (CTD) that directs the cargo to the OM translocon. At least 18 proteins are involved in this still enigmatic process, with some engaged in the post-translational modification of T9SS cargo proteins. Upon translocation across the OM, the CTD is removed by a protease with sortase-like activity and an anionic LPS is attached to the newly formed C-terminus. As a result, a cargo protein could be secreted into the extracellular milieu or covalently attached to the bacterial surface. T9SS is regulated by a two-component system; however, the precise environmental signal that triggers it has not been identified. Exploring unknown systems contributing to bacterial virulence is exciting, as it may eventually lead to new therapeutic strategies. During the past decade, the major components of T9SS were identified, as well as hints suggesting the possible mechanism of action. In addition, the list of characterized cargo proteins is constantly growing. The actual structure of the translocon, situated in the OM of bacteria, remains the least explored area; however, new technical approaches and increasing scientific attention have resulted in a growing body of data. Therefore, we present a compact up-to-date review of this topic.

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The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis

Cited by 54 publications

References 22 publications

Salivary ammonia levels andTannerella forsythiaare associated with rheumatoid arthritis: A cross sectional study

Salivary ammonia levels andTannerella forsythiaare associated with rheumatoid arthritis: A cross sectional study

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

The Type IX Secretion System (T9SS): Highlights and Recent Insights into Its Structure and Function

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