scholarly journals Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Theodoros Goulas ◽  
Danuta Mizgalska ◽  
Irene Garcia-Ferrer ◽  
Tomasz Kantyka ◽  
Tibisay Guevara ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Host Protein ◽  
Peptidylarginine Deiminase ◽  
Bacterial Host

scholarly journals Purification, Characterization, and Sequence Analysis of a Potential Virulence Factor from Porphyromonas gingivalis, Peptidylarginine Deiminase

1999 ◽  
Vol 67 (7) ◽  
pp. 3248-3256 ◽  
Author(s):  
Walker T. McGraw ◽  
Jan Potempa ◽  
David Farley ◽  
James Travis
Keyword(s):  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Limited Proteolysis ◽  
Peptide Hormone ◽  
Neutrophil Function ◽  
Periodontal Pocket ◽  
Significant Activity ◽  
Peptidylarginine Deiminase ◽  
Negative Effects ◽  
Arginine Residues

ABSTRACT The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus byPorphyromonas gingivalis. This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production byP. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55°C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses.

Porphyromonas gingivalis peptidylarginine deiminase substrate specificity

Anaerobe ◽  
2013 ◽  
Vol 23 ◽  
pp. 102-108 ◽  
Author(s):  
Syatirah-Najmi Abdullah ◽  
Elizabeth-Anne Farmer ◽  
Llewellyn Spargo ◽  
Richard Logan ◽  
Neville Gully
Keyword(s):  
Substrate Specificity ◽  
Porphyromonas Gingivalis ◽  
Peptidylarginine Deiminase

Effect of curcumin on growth, biofilm formation and virulence factor gene expression of Porphyromonas gingivalis

Odontology ◽  
2020 ◽  
Vol 109 (1) ◽  
pp. 18-28
Author(s):  
Vijay M. Kumbar ◽  
Malleswara Rao Peram ◽  
Manohar S. Kugaji ◽  
Tejas Shah ◽  
Sanjivani P. Patil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Biofilm Formation ◽  
Factor Gene ◽  
Virulence Factor Gene

scholarly journals Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive Chlamydia trachomatis Biovars

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Michael John Patton ◽  
Chih-Yu Chen ◽  
Chunfu Yang ◽  
Stuart McCorrister ◽  
Chris Grant ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Virulence Factor ◽  
Chlamydial Infection ◽  
Virulence Genes ◽  
Negative Regulation ◽  
Host Protein ◽  
Regulatory Function ◽  
Important Virulence Factor ◽  
Gene Regulatory ◽  
Regulatory Functions

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease.C. trachomatisisolates are classified into 2 biovars—lymphogranuloma venereum (LGV) and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. TheC. trachomatisplasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-curedC. trachomatisserovars A and D (trachoma biovar), a L2 serovar (LGV biovar), and the L2 serovar transformed with a plasmid containing a nonsense mutation inpgp4to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within bothC. trachomatisbiovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF) for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature.IMPORTANCETheChlamydia trachomatisplasmid is an important virulence factor in the pathogenesis of chlamydial infection. It is known that plasmid protein 4 (Pgp4) functions in the transcriptional regulation of the plasmid virulence protein 3 (Pgp3) and multiple chromosomal loci of unknown function. Since many gene regulatory functions can be post-transcriptional, we undertook a comparative proteomic analysis to better understand the plasmid’s role in chlamydial and host protein expression. We report that Pgp4 is a potent and specific master positive regulator of a common core of plasmid and chromosomal virulence genes shared by multipleC. trachomatisserovars. Notably, we show that the plasmid is a negative regulator of the expression of the chlamydial virulence factor CPAF. The plasmid regulation of CPAF is independent of Pgp4 and restricted to aC. trachomatismacrophage-tropic strain. These findings are important because they define a previously unknown role for the plasmid in the pathophysiology of invasive chlamydial infection.

scholarly journals Structural and Functional Analysis of SsaV Cytoplasmic Domain and Variable Linker States in the Context of the InvA-SsaV Chimeric Protein

2021 ◽  
Author(s):  
Jinghua Xu ◽  
Jiuqing Wang ◽  
Aijun Liu ◽  
Yanqing Zhang ◽  
Xiang Gao
Keyword(s):  
Functional Analysis ◽  
Host Cell ◽  
Virulence Factor ◽  
Type Iii Secretion ◽  
Chimeric Protein ◽  
Secretion System ◽  
Bacterial Host ◽  
Gram Negative ◽  
Wide Range ◽  
Host Infection

Type III secretion system (T3SS) is a multicomponent nanomachine and a critical virulence factor for a wide range of Gram-negative bacterial pathogens. It can deliver numbers of effectors into the host cell to facilitate the bacterial host infection.

scholarly journals Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xida Zhao ◽  
Jingbo Liu ◽  
Chong Zhang ◽  
Ning Yu ◽  
Ze Lu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Porphyromonas Gingivalis ◽  
Th17 Cell ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Peptidylarginine Deiminase ◽  
T Helper 17 ◽  
Colon Tissue ◽  
Cell Numbers

AbstractUlcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0−40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31−40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

scholarly journals PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis

2020 ◽  
Author(s):  
Danielle M. Vermilyea ◽  
M. Fata Moradali ◽  
Hey-Min Kim ◽  
Mary E. Davey
Keyword(s):  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Virulence Determinants ◽  
Peptidylarginine Deiminase ◽  
Arginine Metabolism ◽  
Key Factor ◽  
Surface Translocation

Many bacteria switch between a sessile and a motile mode in response to environmental and host-related signals. Porphyromonas gingivalis, an oral anaerobe implicated in the etiology of chronic periodontal disease, has long been described as a non-motile bacterium. Yet, recent studies have shown that under certain conditions, P. gingivalis is capable of surface translocation. Considering these findings, this work aimed to increase our understanding as to how P. gingivalis transitions between sessile growth and surface migration. Here we show that the peptidylarginine deiminase secreted by P. gingivalis (PPAD), an enzyme previously shown to be upregulated during surface translocation and to constrain biofilm formation, promotes surface translocation. In the absence of PPAD, the production of outer membrane vesicles (OMVs) was drastically reduced. In turn, there was a reduction in gingipain-mediated proteolysis and a reduced zone of hydration around the site of inoculation. RNA-Seq and metabolomics analyses also showed that these changes corresponded to a shift in arginine metabolism. Overall, this study provides new evidence for the functional relevance of PPAD and proteases, as well as the importance of PPAD activity in OMV biogenesis and release. Our findings support the model that citrullination is a critical mechanism during lifestyle transition between surface-attached growth and surface translocation by modulating OMV-mediated proteolysis and arginine metabolism. IMPORTANCE Gram-negative bacteria produce nanosized OMVs that are actively released into their surroundings. The oral anaerobe P. gingivalis is prolific in OMV production and many of the proteins packaged in these vesicles are proteolytic or protein modifying enzymes. This includes key virulence determinants, such as the gingipains and PPAD (a unique peptidylarginine deiminase). Here, we show that PPAD activity (citrullination) is involved in OMV biogenesis. The study reveals an unusual mechanism that allows this bacterium to transform its surroundings. Since OMVs are detected in circulation and in systemic tissues, our study also supports the notion that PPAD activity may be a key factor in the correlation between periodontitis and systemic diseases further supporting PPAD as an important therapeutic target.

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