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European Journal of Clinical... Nov 2020Porphyromonas gingivalis, a major subgingival plaque bacterium in periodontitis, has recently attracted much attention as a possible microbial driver in Alzheimer's... (Review)
Review
Porphyromonas gingivalis, a major subgingival plaque bacterium in periodontitis, has recently attracted much attention as a possible microbial driver in Alzheimer's disease. In the present paper, another common neuroinflammatory disease, Parkinson's disease (PD), is discussed. A recent study found major virulence factors of P. gingivalis such as gingipain R1 (RgpA) and lipopolysaccharide in the blood circulation of a PD population. The current review reveals how features such as systemic inflammation, hypercoagulation, presence of amyloid fibrin(ogen) in plasma, and marked ultrastructural changes in platelets, probably induced by P. gingivalis, may affect the development of PD. Several other clinical studies have also demonstrated an association between periodontitis and PD. Even if the risk of periodontal diseases causing neurological disorders needs to be better substantiated, that should not keep us from trying to prevent them by performing careful daily dental hygiene.
Topics: Humans; Parkinson Disease; Porphyromonas gingivalis; Virulence Factors
PubMed: 32564247
DOI: 10.1007/s10096-020-03944-2 -
Trends in Microbiology Jan 2021Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of... (Review)
Review
Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of periodontitis. Transposon sequencing has been employed to define the core essential genome of this bacterium and genes conditionally essential in multiple environments - abscess formation; epithelial colonization; and cigarette smoke toxin exposure; as well as to elucidate genes required for iron acquisition and a functional type 9 secretion system. Validated and predicted protein catabolism genes identified include a combination of established virulence factors and a larger set of seemingly more mundane proteolytic genes. The functions and relevance of genes that share essentiality in multiple disease-relevant conditions are examined. These common stress-related genes may represent particularly attractive therapeutic targets for the control of P. gingivalis infections.
Topics: Animals; Bacterial Proteins; Bacteroidaceae Infections; Genes, Essential; Humans; Porphyromonas gingivalis; Virulence Factors
PubMed: 33071035
DOI: 10.1016/j.tim.2020.09.002 -
Future Microbiology Apr 2012Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the... (Review)
Review
Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets.
Topics: Animals; Bacterial Proteins; Humans; Oxidative Stress; Periodontal Diseases; Porphyromonas gingivalis; Reactive Oxygen Species
PubMed: 22439726
DOI: 10.2217/fmb.12.17 -
Journal of Periodontal Research Feb 2017Porphyromonas gingivalis is considered a major pathogen of chronic periodontitis, which also may be implicated with systemic diseases such as atherosclerosis. Secreted...
BACKGROUND AND OBJECTIVE
Porphyromonas gingivalis is considered a major pathogen of chronic periodontitis, which also may be implicated with systemic diseases such as atherosclerosis. Secreted cysteine proteases, gingipains Rgp and Kgp, are essential for P. gingivalis virulence. Some polyphenols and flavonoids are known to inhibit gingipain activity and interfere with biofilm formation by P. gingivalis. Many bioactive compounds have been isolated from Epimedium species, but availability of these compounds on gingipains and P. gingivalis is still unclear. Therefore, the aim of this study was to evaluate natural products from medical plants to develop a new therapeutic agent against periodontal disease.
MATERIAL AND METHODS
Prenylated flavonoids were isolated from Epimedium species plant using column chromatographies. The inhibitory effect of the prenylated flavonoids against protease activity of gingipains were examined using purified gingipains and fluorogenic substrates. Anti-P. gingivalis activity was evaluated to analyze planktonic growth and biofilm formation in brain heart infusion medium in the presence of the prenylated flavonoids.
RESULTS
We isolated 17 prenylated flavonoids (Limonianin, Epimedokoreanin B, etc.) from Epimedium species. We found that some prenylated flavonoids inhibited gingipain activity in a non-competitive manner with K values at μm order. The prenylated flavonoids also hindered growth and biofilm formation of P. gingivalis, in a manner independent of gingipain inhibition by the compounds.
CONCLUSION
The results indicated an inhibitory effect of the prenylated flavonoids against P. gingivalis and would provide useful information for future development of periodontitis treatment that suppresses gingipains, P. gingivalis growth and biofilm formation.
Topics: Adhesins, Bacterial; Biofilms; Cysteine Endopeptidases; Epimedium; Flavonoids; Gingipain Cysteine Endopeptidases; Porphyromonas gingivalis; Prenylation
PubMed: 26957413
DOI: 10.1111/jre.12372 -
FEMS Microbiology Reviews Jan 2005Porphyromonas gingivalis is a Gram-negative anaerobic bacterium associated with the initiation and progression of adult periodontal disease. Iron is utilized by this... (Review)
Review
Porphyromonas gingivalis is a Gram-negative anaerobic bacterium associated with the initiation and progression of adult periodontal disease. Iron is utilized by this pathogen in the form of heme and has been shown to play an essential role in its growth and virulence. Recently, considerable attention has been given to the characterization of various secreted and surface-associated proteins of P. gingivalis and their contribution to virulence. In particular, the properties of proteins involved in the uptake of iron and heme have been extensively studied. Unlike other Gram-negative bacteria, P. gingivalis does not produce siderophores. Instead it employs specific outer membrane receptors, proteases (particularly gingipains), and lipoproteins to acquire iron/heme. In this review, we will focus on the diverse mechanisms of iron and heme acquisition in P. gingivalis. Specific proteins involved in iron and heme capture will be described. In addition, we will discuss new genes for iron/heme utilization identified by nucleotide sequencing of the P. gingivalis W83 genome. Putative iron- and heme-responsive gene regulation in P. gingivalis will be discussed. We will also examine the significance of heme/hemoglobin acquisition for the virulence of this pathogen.
Topics: Genes, Bacterial; Heme; Iron; Porphyromonas gingivalis; Virulence
PubMed: 15652979
DOI: 10.1016/j.femsre.2004.09.001 -
Applied and Environmental Microbiology Jan 2021Periodontitis is a highly prevalent oral inflammatory disease triggered by dysbiotic subgingival microbiota. For the development of microbiome modulators that can...
Periodontitis is a highly prevalent oral inflammatory disease triggered by dysbiotic subgingival microbiota. For the development of microbiome modulators that can reverse the dysbiotic state and reestablish a health-associated microbiota, a high-throughput multispecies biofilm model is needed. Our aim is to establish a model that resembles a dysbiotic subgingival microbial biofilm by incorporating the major periodontal pathogen into microcosm biofilms cultured from pooled saliva of healthy volunteers. The biofilms were grown for 3, 7, and 10 days and analyzed for their microbial composition by 16S rRNA gene amplicon sequencing as well as measurement of dipeptidyl peptidase IV (DPP4) activity and butyric acid production. The addition of increased its abundance in saliva-derived microcosm biofilms from 2.7% on day 3 to >50% on day 10, which significantly reduced the Shannon diversity but did not affect the total number of operational taxonomic units (OTUs). The -enriched biofilms displayed altered microbial composition as revealed by principal-component analysis and reduced interactions among microbial species. Moreover, these biofilms exhibited enhanced DPP4 activity and butyric acid production. In conclusion, by adding to saliva-derived microcosm biofilms, we established an pathogen-enriched dysbiotic microbiota which resembles periodontitis-associated subgingival microbiota in terms of increased abundance and higher DPP4 activity and butyric acid production. This model may allow for investigating factors that accelerate or hinder a microbial shift from symbiosis to dysbiosis and for developing microbiome modulation strategies. In line with the new paradigm of the etiology of periodontitis, an inflammatory disorder initiated by dysbiotic subgingival microbiota, novel therapeutic strategies have been proposed targeting reversing dysbiosis and restoring host-compatible microbiota rather than eliminating the biofilms unselectively. Thus, appropriate laboratory models are required to evaluate the efficacy of potential microbiome modulators. In the present study, we used the easily obtainable saliva as an inoculum, spiked the microcosm biofilms with the periodontal pathogen , and obtained a -enriched microbiota, which resembles the pathogen-enriched subgingival microbiota in severe periodontitis. This biofilm model circumvents the difficulties encountered when using subgingival plaque as the inoculum and achieves microbiota in a dysbiotic state in a controlled and reproducible manner, which is required for high-throughput and large-scale evaluation of strategies that can potentially modulate microbial ecology.
Topics: Biofilms; Butyric Acid; Dipeptidyl Peptidase 4; Dysbiosis; Gingiva; Humans; Microbiota; Porphyromonas gingivalis; RNA, Ribosomal, 16S; Saliva
PubMed: 33158898
DOI: 10.1128/AEM.02371-20 -
Microbiology Spectrum Feb 2022Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with...
Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with findings that include the O-glycosylation motif, the structure of the O-glycans in a few species, and an extensive O-glycoproteome analysis in Tannerella forsythia. However, O-glycosylation has not yet been confirmed in P. gingivalis. We therefore used glycoproteomics approaches including partial deglycosylation with trifluoromethanesulfonic acid as well as both HILIC and FAIMS based glycopeptide enrichment strategies leading to the identification of 257 putative glycosylation sites in 145 glycoproteins. The sequence of the major O-glycan was elucidated to be HexNAc-HexNAc(P-Gro-[Ac])-dHex-Hex-HexA-Hex(dHex). Western blot analyses of mutants lacking the glycosyltransferases PGN_1134 and PGN_1135 demonstrated their involvement in the biosynthesis of the glycan while mass spectrometry analysis of the truncated O-glycans suggested that PGN_1134 and PGN_1135 transfer the two HexNAc sugars. Interestingly, a strong bias against the O-glycosylation of abundant proteins exposed to the cell surface such as abundant T9SS cargo proteins, surface lipoproteins, and outer membrane β-barrel proteins was observed. In contrast, the great majority of proteins associated with the inner membrane or periplasm were glycosylated irrespective of their abundance. The P. gingivalis O-glycosylation system may therefore function to establish the desired physicochemical properties of the periplasm. 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. This study has for the first time demonstrated the presence of O-linked glycosylation in this organism by determining the basic structure of the O-glycans and identifying 257 glycosylation sites in 145 proteins. It was found that most proteins exposed to the periplasm were O-glycosylated; however, the abundant surface exposed proteins were not. The O-glycans consisted of seven monosaccharides and a glycerol phosphate with 0-2 acetyl groups. These glycans are likely to have a stabilizing role to the proteins that bear them and must be taken into account when the proteins are produced in heterologous organisms.
Topics: Amino Acid Motifs; Bacterial Proteins; Carbohydrate Sequence; Glycoproteins; Glycosylation; Humans; Polysaccharides; Porphyromonas gingivalis
PubMed: 34985300
DOI: 10.1128/spectrum.01502-21 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Feb 2021(), a Gram-negative oral anaerobe, is considered to be a major pathogenic agent involved in the onset and progression of chronic periodontitis. must be able to... (Review)
Review
(), a Gram-negative oral anaerobe, is considered to be a major pathogenic agent involved in the onset and progression of chronic periodontitis. must be able to perceive and respond to the complicated changes in host to survive the environmental challenges, in which the two-component signal transduction systems (TCSs) play critical roles by connecting input signals to cellular physiological output. Canonical TCS consists of a sensor histidine kinase and a cognate response regulator that functions via a phosphorylation cascade. In this review, the roles of TCSs in were demonstrated by illustrating the target genes and modulation modes, which may help elucidate the underlying mechanisms in future studies.
Topics: Phosphorylation; Porphyromonas gingivalis; Signal Transduction
PubMed: 33723942
DOI: 10.7518/hxkq.2021.01.013 -
International Journal of Molecular... Dec 2021IgA nephropathy (IgAN) has been considered to have a relationship with infection in the tonsil, because IgAN patients often manifest macro hematuria just after...
IgA nephropathy (IgAN) has been considered to have a relationship with infection in the tonsil, because IgAN patients often manifest macro hematuria just after tonsillitis. In terms of oral-area infection, the red complex of periodontal bacteria ( (), and ) is important, but the relationship between these bacteria and IgAN remains unknown. In this study, the prevalence of the red complex of periodontal bacteria in tonsil was compared between IgAN and tonsillitis patients. The pathogenicity of IgAN induced by was confirmed by the mice model treated with this bacterium. The prevalence of and in IgAN patients was significantly higher than that in tonsillitis patients ( < 0.001 and < 0.05, respectively). A total of 92% of tonsillitis patients were free from red complex bacteria, while only 48% of IgAN patients had any of these bacteria. Nasal administration of in mice caused mesangial proliferation ( < 0.05 at days 28a nd 42; < 0.01 at days 14 and 56) and IgA deposition ( < 0.001 at day 42 and 56 after administration). Scanning-electron-microscopic observation revealed that a high-density Electron-Dense Deposit was widely distributed in the mesangial region in the mice kidneys treated with . These findings suggest that is involved in the pathogenesis of IgAN.
Topics: Adult; Animals; DNA, Bacterial; Disease Models, Animal; Female; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Kidney; Male; Mice; Middle Aged; Porphyromonas gingivalis; Tannerella forsythia; Tonsillitis; Young Adult
PubMed: 34884826
DOI: 10.3390/ijms222313022 -
Indian Journal of Dental Research :... 2011Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of... (Review)
Review
Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of periodontal vaccine would not only prevent and modulate periodontal disease, but also enhance the quality of life of people for whom periodontal treatment cannot be easily obtained. The aim of the research should be development of a multispecies vaccine targeting the four prime periodontal pathogens, viz. Porphyromonas gingivalis, T. forsythus, T. denticola and A. comitans. Success is still elusive in case of periodontal vaccine due to the complex etiopathogenesis of the disease.
Topics: Aggregatibacter actinomycetemcomitans; Bacterial Proteins; Bacterial Vaccines; Bacteroides; Humans; Immunization; Immunization, Passive; Periodontal Diseases; Porphyromonas gingivalis; Treponema denticola
PubMed: 22406716
DOI: 10.4103/0970-9290.93459