scholarly journals Characterization of the O-Glycoproteome of Porphyromonas gingivalis

2022 ◽  
Author(s):  
Paul D. Veith ◽  
Mikio Shoji ◽  
Nichollas E. Scott ◽  
Eric C. Reynolds
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
Thermodynamic Stability ◽  
Protein Function ◽  
Protein Glycosylation ◽  
Content Type ◽  
Severe Periodontal Disease

Porphyromonas gingivalis is an oral pathogen primarily associated with severe periodontal disease and further associated with rheumatoid arthritis, dementia, cardiovascular disease, and certain cancers. Protein glycosylation can be important for a variety of reasons including protein function, solubility, protease resistance, and thermodynamic stability.

scholarly journals Functional Analysis of Porphyromonas gingivalis W83 CRISPR-Cas Systems

2015 ◽  
Vol 197 (16) ◽  
pp. 2631-2641 ◽  
Author(s):  
Michał Burmistrz ◽  
Bartosz Dudek ◽  
Dominika Staniec ◽  
Jose Ignacio Rodriguez Martinez ◽  
Matthias Bochtler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Porphyromonas Gingivalis ◽  
Human Pathogen ◽  
Significant Similarity ◽  
Content Type ◽  
Genetic Elements ◽  
Protospacer Adjacent Motif ◽  
Unique System

ABSTRACTThe CRISPR-Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) system provides prokaryotic cells with an adaptive and heritable immune response to foreign genetic elements, such as viruses, plasmids, and transposons. It is present in the majority ofArchaeaand almost half of species ofBacteria.Porphyromonas gingivalisis an important human pathogen that has been proven to be an etiological agent of periodontitis and has been linked to systemic conditions, such as rheumatoid arthritis and cardiovascular disease. At least 95% of clinical strains ofP. gingivaliscarry CRISPR arrays, suggesting that these arrays play an important functionin vivo. Here we show that all four CRISPR arrays present in theP. gingivalisW83 genome are transcribed. For one of the arrays, we demonstratein vivoactivity against double-stranded DNA constructs containing protospacer sequences accompanied at the 3′ end by an NGG protospacer-adjacent motif (PAM). Most of the 44 spacers present in the genome ofP. gingivalisW83 share no significant similarity with any known sequences, although 4 spacers are similar to sequences from bacteria found in the oral cavity and the gastrointestinal tract. Four spacers match genomic sequences of the host; however, none of these is flanked at its 3′ terminus by the appropriate PAM element.IMPORTANCEThe CRISPR-Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) system is a unique system that provides prokaryotic cells with an adaptive and heritable immunity. In this report, we show that the CRISPR-Cas system ofP. gingivalis, an important human pathogen associated with periodontitis and possibly also other conditions, such as rheumatoid arthritis and cardiovascular disease, is active and provides protection from foreign genetic elements. Importantly, the data presented here may be useful for better understanding the communication between cells in larger bacterial communities and, consequently, the process of disease development and progression.

scholarly journals Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs in the Porphyromonas gingivalis CRISPR-Cas I-C System

2017 ◽  
Vol 199 (23) ◽  
Author(s):  
Michal Burmistrz ◽  
Jose Ignacio Rodriguez Martinez ◽  
Daniel Krochmal ◽  
Dominika Staniec ◽  
Krzysztof Pyrc
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Porphyromonas Gingivalis ◽  
Aspiration Pneumonia ◽  
Repeat Sequence ◽  
Type I ◽  
Content Type ◽  
Short Palindromic Repeat ◽  
Cellular Defenses ◽  
Clinical Conditions

ABSTRACT The CRISPR-Cas (clustered regularly interspaced short palindromic repeat–CRISPR-associated protein) system is unique to prokaryotes and provides the majority of bacteria and archaea with immunity against nucleic acids of foreign origin. CRISPR RNAs (crRNAs) are the key element of this system, since they are responsible for its selectivity and effectiveness. Typical crRNAs consist of a spacer sequence flanked with 5′ and 3′ handles originating from repeat sequences that are important for recognition of these small RNAs by the Cas machinery. In this investigation, we studied the type I-C CRISPR-Cas system in Porphyromonas gingivalis, a human pathogen associated with periodontitis, rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. We demonstrated the importance of the 5′ handle for crRNA recognition by the effector complex and consequently activity, as well as secondary trimming of the 3′ handle, which was not affected by modifications of the repeat sequence. IMPORTANCE Porphyromonas gingivalis, a clinically relevant Gram-negative, anaerobic bacterium, is one of the major etiologic agents of periodontitis and has been linked with the development of other clinical conditions, including rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. The presented results on the biogenesis and functions of crRNAs expand our understanding of CRISPR-Cas cellular defenses in P. gingivalis and of horizontal gene transfer in bacteria.

scholarly journals POS0068 HIGH LEVELS OF PORPHYROMONAS GINGIVALIS AND PREVOTELLA INTERMEDIA ANTIBODIES IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 240.2-241
Author(s):  
F. Zekre ◽  
R. Cimaz ◽  
M. Paul ◽  
J. L. Stephan ◽  
S. Paul ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
Joint Disease ◽  
Control Group ◽  
Prevotella Intermedia ◽  
Igg Antibodies ◽  
Idiopathic Juvenile Arthritis ◽  
High Level

Background:Idiopathic juvenile arthritis (JIA) is a heterogeneous group of pathologies whose origin remains unknown at present (1). They are characterised by a systemic inflammatory and joint disease affecting children under 16 years of age. The current classification groups the different forms of JIA into 7 distinct entities (systemic forms, polyarticular forms with or without rheumatoid factors, oligoarticular forms, inflammatory arthritis associated with enthesopathies (ERA), arthritis associated with psoriasis and unclassifiable arthritis). Exact etiology of JIA is still unknown. To date, the various hypotheses put forward on the occurrence of JIAs integrate the genetic and environmental framework.The link between periodontal disease and rheumatoid arthritis (RA) is largely reported. Recently, Porphyromonas gingivalis (P. gingivalis) infection explained the occurrence of arthritis in rodent and in RA (2). Several studies mention the beneficial effect of P. gingivalis treatment on disease activity.Currently, there are very few studies on the prevalence of P. gingivalis in patients with JIA and the possible involvement of the germ in the development of inflammatory joint diseases in the pediatric population(3)(4).Objectives:The objective of our study is to determine presence of high IgG antibodies against P. gingivalis and Prevotella Intermedia in a cohort of patients with JIA compared to a control population and to determine variation of level according to sub-classes of JIA.Methods:Sera were obtained from 101 patients satisfying the ILAR classification criteria for JIA and in 25 patients with two other dysimmune disorders (type 1 diabetes and juvenile inflammatory bowel disease). Level of IgG antibodies against P. gingivalis and Prevotella Intermedia were obtained by homemade ELISA already used previously (5).Results:In the JIA group, major children were oligarthritis (47.5%), polyarthritis represents 31.7% of JIAs, ERA and systemic forms of JIA are respectively 9 and 11%. For the control group, 10 (40%) children had diabetes and 15 (60%) had IBD.Levels of anti-P. gingivalis anti-Prevotella Intermedia antibodies were higher in AJI group compared at control groups (P<0.01, P<0.05). Theses difference are mainly related to oligoarthritis and ERA subsets for both P. gingivalis and Prevotella Intermedia.Figure 1.Relative titer of antibodies to P. gingivalis and anti Prevotella intermedia. *: P<0.05; **: P<0.01; ***: P<0.001. P. gingivalis (control vs oligoarthritis p= 0.0032. control vs ERA p= 0.0092). Prevotella intermedia (control vs oligoarthritis p= 0.0194. control vs ERA p= 0.0039).Conclusion:We confirmed high level of anti-P. gingivalis and anti-Prevotella intermedia antibodies in JIA compared to other inflammatory disorders. For the first time, we observed that this high level was mainly in oligoarthritis and ERA. Further investigations are required to investigate involvement of oral dysbiosis in AJI pathogenesis. As observed in RA, it could be a new way to integrate in JIA therapy management.References:[1]Thatayatikom A, De Leucio A. Juvenile Idiopathic Arthritis (JIA). StatPearls Publishing; 2020[2]Cheng Z, Meade J, Mankia K, Emery P, Devine DA. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):19–30.[3]Romero-Sánchez C, Malagón C, Vargas C, Fernanda Torres M, Moreno LC, Rodríguez C, et al. Porphyromonas Gingivalis and IgG1 and IgG2 Subclass Antibodies in Patients with Juvenile Idiopathic Arthritis. J Dent Child Chic Ill. 2017 May 15;84(2):72–9.[4]Lange L, Thiele GM, McCracken C, Wang G, Ponder LA, Angeles-Han ST, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016 Feb 9[5]Rinaudo-Gaujous M, Blasco-Baque V, Miossec P, Gaudin P, Farge P, Roblin X, et al. Infliximab Induced a Dissociated Response of Severe Periodontal Biomarkers in Rheumatoid Arthritis Patients. J Clin Med. 2019 May 26;8(5).Disclosure of Interests:None declared.

scholarly journals Targeting the HUβ Protein PreventsPorphyromonas gingivalisfrom Entering into Preexisting Biofilms

2018 ◽  
Vol 200 (11) ◽  
pp. e00790-17 ◽  
Author(s):  
Christopher J. Rocco ◽  
Lauren O. Bakaletz ◽  
Steven D. Goodman
Keyword(s):  
Oral Cavity ◽  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
The United States ◽  
Extracellular Dna ◽  
Bacterial Biofilms ◽  
Oral Streptococci ◽  
Content Type ◽  
Oral Streptococcus ◽  
Streptococcal Species

ABSTRACTThe oral cavity is home to a wide variety of bacterial species, both commensal, such as various streptococcal species, and pathogenic, such asPorphyromonas gingivalis, one of the main etiological agents of periodontal disease. Our understanding of how these bacteria ultimately cause disease is highly dependent upon understanding how they coexist and interact with one another in biofilm communities and the mechanisms by which biofilms are formed. Our research has demonstrated that the DNABII family of DNA-binding proteins are important components of the extracellular DNA (eDNA)-dependent matrix of bacterial biofilms and that sequestering these proteins via protein-specific antibodies results in the collapse of the biofilm structure and release of the resident bacteria. While the high degree of similarity among the DNABII family of proteins has allowed antibodies derived against specific DNABII proteins to disrupt biofilms formed by a wide range of bacterial pathogens, the DNABII proteins ofP. gingivalishave proven to be antigenically distinct, allowing us to determine if we can use anti-P. gingivalisHUβ antibodies to specifically target this species for removal from a mixed-species biofilm. Importantly, despite forming homotypic biofilmsin vitro,P. gingivalismust enter preexisting biofilmsin vivoin order to persist within the oral cavity. The data presented here indicate that antibodies derived against theP. gingivalisDNABII protein, HUβ, reduce by half the amount ofP. gingivalisorganisms entering into preexisting biofilm formed by four oral streptococcal species. These results support our efforts to develop methods for preventing and treating periodontal disease.IMPORTANCEPeriodontitis is one of the most prevalent chronic infections, affecting 40 to 50% of the population of the United States. The root cause of periodontitis is the presence of bacterial biofilms within the gingival space, withPorphyromonas gingivalisbeing strongly associated with the development of the disease. Periodontitis also increases the risk of secondary conditions and infections such as atherosclerosis and infective endocarditis caused by oral streptococci. To induce periodontitis,P. gingivalisneeds to incorporate into preformed biofilms, with oral streptococci being important binding partners. Our research demonstrates that targeting DNABII proteins with an antibody disperses oral streptococcus biofilm and preventsP. gingivalisentry into oral streptococcus biofilm. These results suggest potential therapeutic treatments for endocarditis caused by streptococci as well as periodontitis.

Non-neoplastic expanding lesions of the vermis cerebelli

1972 ◽  
Vol 37 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Göran Sundbärg ◽  
Arne Brun ◽  
Hans-Olof Efsing ◽  
Nils Lundberg
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Clinical Significance ◽  
Content Type ◽  
Postoperative Course ◽  
Histological Picture ◽  
Roentgen Diagnosis ◽  
Perifocal Edema ◽  
History Of ◽  
Fine Print

✓ This report describes the clinical, roentgenological, and histopathological findings in 13 patients in whom the preoperative roentgen diagnosis was tumor of the vermis cerebelli but in whom no neoplasm was found at operation nor suggested by postoperative course. There was a striking clinical conformity; the majority of the patients were between 50 and 70 years of age, had a history of rheumatoid arthritis and/or cardiovascular disease, and a histological picture characterized by small cavernous-capillary hemangiomas and spongiosis indicating perifocal edema. The pathogenesis and clinical significance of the lesions are discussed.

scholarly journals Gingipains from the Periodontal Pathogen Porphyromonas gingivalis Play a Significant Role in Regulation of Angiopoietin 1 and Angiopoietin 2 in Human Aortic Smooth Muscle Cells

2015 ◽  
Vol 83 (11) ◽  
pp. 4256-4265 ◽  
Author(s):  
Boxi Zhang ◽  
Hazem Khalaf ◽  
Allan Sirsjö ◽  
Torbjörn Bengtsson
Keyword(s):  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Porphyromonas Gingivalis ◽  
Wild Type ◽  
Content Type ◽  
Aortic Smooth Muscle ◽  
Angiopoietin 2 ◽  
Angiopoietin 1

ABSTRACTAngiopoietin 1 (Angpt1) and angiopoietin 2 (Angpt2) are the ligands of tyrosine kinase (Tie) receptors, and they play important roles in vessel formation and the development of inflammatory diseases, such as atherosclerosis.Porphyromonas gingivalisis a Gram-negative periodontal bacterium that is thought to contribute to the progression of cardiovascular disease. The aim of this study was to investigate the role ofP. gingivalisinfection in the modulation of Angpt1 and Angpt2 in human aortic smooth muscle cells (AoSMCs). We exposed AoSMCs to wild-type (W50 and 381), gingipain mutant (E8 and K1A), and fimbrial mutant (DPG-3 and KRX-178)P. gingivalisstrains and to different concentrations of tumor necrosis factor (TNF). The atherosclerosis risk factor TNF was used as a positive control in this study. We found thatP. gingivalis(wild type, K1A, DPG3, and KRX178) and TNF upregulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited byP. gingivalisand TNF. However, the RgpAB mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical forP. gingivalisinduction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation. This study demonstrates that gingipains are crucial to the ability ofP. gingivalisto markedly increase the expressed Angpt2/Angpt1 ratio in AoSMCs, which determines the regulatory role of angiopoietins in angiogenesis and their involvement in the development of atherosclerosis. These findings further support the association between periodontitis and cardiovascular disease.

scholarly journals Genotypic and Phenotypic Characterization of theO-Linked Protein Glycosylation System Reveals High Glycan Diversity in Paired Meningococcal Carriage Isolates

2018 ◽  
Vol 200 (16) ◽  
Author(s):  
Bente Børud ◽  
Guro K. Bårnes ◽  
Ola Brønstad Brynildsrud ◽  
Elisabeth Fritzsønn ◽  
Dominique A. Caugant
Keyword(s):  
Neisseria Meningitidis ◽  
Phase Variation ◽  
Protein Glycosylation ◽  
Phase Variable ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Variable Expression ◽  
Evolutionary Forces ◽  
Strain Collection

ABSTRACTSpecies within the genusNeisseriadisplay significant glycan diversity associated with theO-linked protein glycosylation (pgl) systems due to phase variation and polymorphic genes and gene content. The aim of this study was to examine in detail thepglgenotype and glycosylation phenotype in meningococcal isolates and the changes occurring during short-term asymptomatic carriage. Paired meningococcal isolates derived from 50 asymptomatic meningococcal carriers, taken about 2 months apart, were analyzed with whole-genome sequencing. TheO-linked protein glycosylation genes were characterized in detail using the Genome Comparator tool at the https://pubmlst.org/ database. Immunoblotting with glycan-specific antibodies (Abs) was used to investigate the protein glycosylation phenotype. All majorpgllocus polymorphisms identified inNeisseria meningitidisto date were present in our isolate collection, with the variable presence ofpglGandpglH, both in combination with eitherpglBorpglB2. We identified significant changes and diversity in thepglgenotype and/or glycan phenotype in 96% of the paired isolates. There was also a high degree of glycan microheterogeneity, in which different variants of glycan structures were found at a given glycoprotein. The main mechanism responsible for the observed differences was phase-variable expression of the involved glycosyltransferases and theO-acetyltransferase. To our knowledge, this is the first characterization of thepglgenotype and glycosylation phenotype in a larger strain collection. This report thus provides important insight into glycan diversity inN. meningitidisand into the phase variability changes that influence the expressed glycoform repertoire during meningococcal carriage.IMPORTANCEBacterial meningitis is a serious global health problem, and one of the major causative organisms isNeisseria meningitidis, which is also a common commensal in the upper respiratory tract of healthy humans. In bacteria, numerous loci involved in biosynthesis of surface-exposed antigenic structures that are involved in the interaction between bacteria and host are frequently subjected to homologous recombination and phase variation. These mechanisms are well described inNeisseria, and phase variation provides the ability to change these structures reversibly in response to the environment. Protein glycosylation systems are becoming widely identified in bacteria, and yet little is known about the mechanisms and evolutionary forces influencing glycan composition during carriage and disease.

scholarly journals Draft Whole-Genome Sequences of Periodontal Pathobionts Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia Contain Phase-Variable Restriction-Modification Systems

2017 ◽  
Vol 5 (46) ◽  
Author(s):  
Richard D. Haigh ◽  
Liam A. Crawford ◽  
Joseph D. Ralph ◽  
Joseph J. Wanford ◽  
Sonia R. Vartoukian ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
Disease Process ◽  
Oral Bacteria ◽  
Host Responses ◽  
Prevotella Intermedia ◽  
Phase Variable ◽  
Genome Sequences ◽  
Tannerella Forsythia ◽  
Content Type

ABSTRACT Periodontal disease comprises mild to severe inflammatory host responses to oral bacteria that can cause destruction of the tooth-supporting tissue. We report genome sequences for 18 clinical isolates of Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia, Gram-negative obligate anaerobes that play a role in the periodontal disease process.

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