scholarly journals Immunization with Porphyromonas gingivalis Capsular Polysaccharide Prevents P. gingivalis-Elicited Oral Bone Loss in a Murine Model

2003 ◽  
Vol 71 (4) ◽  
pp. 2283-2287 ◽  
Author(s):  
Dario Gonzalez ◽  
Arthur O. Tzianabos ◽  
Caroline A. Genco ◽  
Frank C. Gibson
Keyword(s):  
Bone Loss ◽  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Murine Model ◽  
Capsular Polysaccharide ◽  
Vaccine Candidate ◽  
Immunoglobulin M ◽  
Periodontal Pathogen ◽  
Vaccine Potential ◽  
Important Virulence Factor

ABSTRACT The capsular polysaccharide (CPS) of the periodontal pathogen Porphyromonas gingivalis is an important virulence factor for this organism. We purified P. gingivalis CPS, immunized mice with this antigen, and assessed the vaccine potential of P. gingivalis CPS by using the murine oral challenge model. Animals immunized with P. gingivalis CPS developed elevated levels of immunoglobulin M (IgM) and IgG in serum that reacted with whole P. gingivalis organisms. The mice immunized with P. gingivalis CPS were protected from P. gingivalis-elicited oral bone loss. These data demonstrate that P. gingivalis CPS is a vaccine candidate for prevention of P. gingivalis-elicited oral bone loss.

scholarly journals A Porphyromonas gingivalis Capsule-Conjugate Vaccine Protects From Experimental Oral Bone Loss

2021 ◽  
Vol 2 ◽  
Author(s):  
Fernanda G. Rocha ◽  
Aym Berges ◽  
Angie Sedra ◽  
Shirin Ghods ◽  
Neeraj Kapoor ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Conjugate Vaccine ◽  
Porphyromonas Gingivalis ◽  
Capsular Polysaccharide ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Bone Destruction ◽  
Effective Vaccine ◽  
Preclinical Model

Periodontal diseases are chronic inflammatory diseases of the periodontium that result in progressive destruction of the soft and hard tissues supporting the teeth, and it is the most common cause of tooth loss among adults. In the US alone, over 100 million individuals are estimated to have periodontal disease. Subgingival bacteria initiate and sustain inflammation, and, although several bacteria have been associated with periodontitis, Porphyromonas gingivalis has emerged as the key etiological organism significantly contributing to the disease. Currently, intensive clinical maintenance strategies are deployed to mitigate the further progression of disease in afflicted individuals; however, these treatments often fail to stop disease progression, and, as such, the development of an effective vaccine for periodontal disease is highly desirable. We generated a conjugate vaccine, comprising of the purified capsular polysaccharide of P. gingivalis conjugated to eCRM®, a proprietary and enhanced version of the CRM197 carrier protein with predetermined conjugation sites (Pg-CV). Mice immunized with alum adjuvanted Pg-CV developed robust serum levels of whole organism-specific IgG in comparison to animals immunized with unconjugated capsular polysaccharide alone. Using the murine oral bone loss model, we observed that mice immunized with the capsule-conjugate vaccine were significantly protected from the effects of P. gingivalis-elicited oral bone loss. Employing a preclinical model of infection-elicited oral bone loss, our data support that a conjugate vaccine incorporating capsular polysaccharide antigen is effective in reducing the main clinical endpoint of periodontal disease—oral bone destruction. Further development of a P. gingivalis capsule-based conjugate vaccine for preventing periodontal diseases is supported.

scholarly journals Using Tn-seq To Identify Pigmentation-Related Genes of Porphyromonas gingivalis: Characterization of the Role of a Putative Glycosyltransferase

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
Brian A. Klein ◽  
Louis P. Cornacchione ◽  
Marisha Collins ◽  
Michael H. Malamy ◽  
Margaret J. Duncan ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Massively Parallel Sequencing ◽  
Trna Synthetase ◽  
Mutant Library ◽  
Content Type ◽  
Intergenic Regions ◽  
Complete Survey ◽  
Important Virulence Factor ◽  
Transposon Insertions

ABSTRACT Cellular pigmentation is an important virulence factor of the oral pathogen Porphyromonas gingivalis. Pigmentation has been associated with many bacterial functions, including but not limited to colonization, maintaining a local anaerobic environment by binding oxygen molecules, and defense against reactive oxygen species (ROS) produced by immune cells. Pigmentation-associated loci identified to date have involved lipopolysaccharide, fimbriae, and heme acquisition and processing. We utilized a transposon mutant library of P. gingivalis strain ATCC 33277 and screened for pigmentation-defective colonies using massively parallel sequencing of the transposon junctions (Tn-seq) to identify genes involved in pigmentation. Transposon insertions at 235 separate sites, located in 67 genes and 15 intergenic regions, resulted in altered pigmentation: 7 of the genes had previously been shown to be involved in pigmentation, while 75 genes and intergenic regions had not. To further confirm identification, we generated a smaller transposon mutant library in P. gingivalis strain W83 and identified pigment mutations in several of the same loci as those identified in the screen in ATCC 33277 but also eight that were not identified in the ATCC 33277 screen. PGN_0361/PG_0264, a putative glycosyltransferase gene located between two tRNA synthetase genes and adjacent to a miniature inverted-repeat transposable element, was identified in the Tn-seq screen and then verified through targeted deletion and complementation. Deletion mutations in PGN_0361/PG_0264 glycosyltransferase abolish pigmentation, modulate gingipain protease activity, and alter lipopolysaccharide. The mechanisms of involvement in pigmentation for other loci identified in this study remain to be determined, but our screen provides the most complete survey of genes involved in pigmentation to date. IMPORTANCE P. gingivalis has been implicated in the onset and progression of periodontal disease. One important virulence factor is the bacterium's ability to produce pigment. Using a transposon library, we were able to identify both known and novel genes involved in pigmentation of P. gingivalis. We identified a glycosyltransferase, previously not associated with pigmentation, that is required for pigmentation and determined its mechanism of involvement. A better understanding of the genes involved in pigmentation may lead to new insights into the complex mechanisms involved in this important virulence characteristic and could facilitate development of novel therapeutics.

scholarly journals Porphyromonas gingivalis Genes Involved in fimA Regulation

2004 ◽  
Vol 72 (2) ◽  
pp. 651-658 ◽  
Author(s):  
Hua Xie ◽  
Natalia Kozlova ◽  
Richard J. Lamont
Keyword(s):  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Dental Plaque ◽  
Posttranscriptional Regulation ◽  
Regulation Mechanism ◽  
Surface Molecule ◽  
Null Mutant ◽  
Differential Display Pcr ◽  
Important Virulence Factor ◽  
Plaque Biofilm

ABSTRACT Porphyromonas gingivalis is an important component of the complex plaque biofilm that is a direct precursor of periodontal disease. The major fimbriae are required for attachment to oral surfaces and are an important virulence factor. Fimbrillin (FimA) expression in P. gingivalis is inhibited by surface molecule of Streptococcus cristatus, an early colonizer of dental plaque. In this study, differential display PCR was used to identify P. gingivalis genes that are regulated in response to S. cristatus. Of several differentially expressed genes, pg2131 and pg2167 were upregulated by S. cristatus signaling molecules. A null mutant of pg2167 did not transcriptionally regulate fimA following exposure to S. cristatus. In fact, fimA transcription was enhanced in the pg2167 mutant, suggesting that pg2167 may act to repress fimA expression. In contrast, a mutation in pg2131 did not affect transcription of fimA in the presence of S. cristatus. However, production of fimbrillin was significantly diminished in the pg2131 mutant, implicating involvement in posttranscriptional regulation in fimbriation. These data suggest that P. gingivalis fimbriation is controlled by more than one regulation mechanism, involving both transcriptional and posttranscriptional processes.

scholarly journals Molecular Mechanism for the Spontaneous Generation of Pigmentless Porphyromonas gingivalis Mutants

1999 ◽  
Vol 67 (9) ◽  
pp. 4926-4930 ◽  
Author(s):  
Wen Chen ◽  
Howard K. Kuramitsu
Keyword(s):  
Enzyme Activity ◽  
Molecular Mechanism ◽  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Dna Sequences ◽  
Protease Activity ◽  
Periodontal Diseases ◽  
Spontaneous Generation ◽  
Hemoglobin Binding ◽  
Important Virulence Factor

ABSTRACT Porphyromonas gingivalis is one of the pathogens associated with periodontal diseases, and its protease activity has been implicated as an important virulence factor. Kgp is the major Lys-gingipain protease of P. gingivalis and appears to be involved not only in enzyme activity but also in hemagglutination and the pigmented phenotype due to heme accumulation and/or hemoglobin binding. However, little information concerning the molecular mechanism for the spontaneous generation of pigmentless P. gingivalismutants is currently available. In this study, several spontaneous pigmentless mutants of P. gingivalis were isolated and characterized. The results revealed that a portion of thekgp gene had been deleted from the chromosomes of the pigmentless mutants. This deletion appears to result from recombination between the highly homologous DNA sequences encoding the adhesin domains of the tandemly arranged hagA and kgpgenes on the chromosomes of P. gingivalis strains.

scholarly journals Porphyromonas gingivalis-Specific Immunoglobulin G Prevents P. gingivalis-Elicited Oral Bone Loss in a Murine Model

2004 ◽  
Vol 72 (4) ◽  
pp. 2408-2411 ◽  
Author(s):  
Frank C. Gibson ◽  
Dario A. Gonzalez ◽  
Jodie Wong ◽  
Caroline Attardo Genco
Keyword(s):  
Bone Loss ◽  
Porphyromonas Gingivalis ◽  
Murine Model ◽  
Immunoglobulin G ◽  
Active Immunization ◽  
Whole Cell ◽  
Specific Immunoglobulin ◽  
Chamber Model ◽  
Passive Antibody Transfer

ABSTRACT Active immunization with Porphyromonas gingivalis whole-cell preparations has been shown to prevent P. gingivalis infection and oral bone loss. Employing passive antibody transfer and opsonization, we demonstrate with this study that immunization-elicited P. gingivalis-specific immunoglobulin G facilitates clearance of P. gingivalis in a subcutaneous chamber model and prevents P. gingivalis-elicited oral bone loss.

Paracoccidioides brasiliensis 14-3-3 protein is important for virulence in a murine model

2018 ◽  
Vol 57 (7) ◽  
pp. 900-904
Author(s):  
Caroline Maria Marcos ◽  
Haroldo Cesar de Oliveira ◽  
Patricia Akemi Assato ◽  
Cleverton Roberto de Andrade ◽  
Ana Marisa Fusco-Almeida ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Murine Model ◽  
Pulmonary Infection ◽  
Paracoccidioides Brasiliensis ◽  
Yeast Cells ◽  
Fungal Burden ◽  
Important Virulence Factor

AbstractThe Paracoccidioides brasiliensis strain downregulated the expression of adhesin Pb14-3-3 (Pb14-3-3 aRNA) was evaluated in a murine model of paracoccidioidomycosis (PCM). Pb14-3-3 aRNA displays attenuated virulence and triggered the formation of fewer granulomas by lowering the fungal burden in the lungs. Additionally, the Pb14-3-3 aRNA showed more elongated yeast cells and less ability to induce pneumocytes apoptosis in vitro. Our results show that 14-3-3 is an important virulence factor in P. brasiliensis-induced pulmonary infection.

scholarly journals HGP44 Induces Protection against Porphyromonas gingivalis-Induced Alveolar Bone Loss in Mice

2011 ◽  
Vol 18 (5) ◽  
pp. 888-891 ◽  
Author(s):  
Kyotaro Muramatsu ◽  
Eitoyo Kokubu ◽  
Takahiko Shibahara ◽  
Katsuji Okuda ◽  
Kazuyuki Ishihara
Keyword(s):  
Bone Loss ◽  
Protective Effect ◽  
Porphyromonas Gingivalis ◽  
Murine Model ◽  
Alveolar Bone ◽  
Dna Vaccines ◽  
Alveolar Bone Loss ◽  
Content Type ◽  
Candidate Antigen

ABSTRACTThe protective effect of DNA vaccines expressing the Arg-gingipain A domain against bone loss induced byPorphyromonas gingivalisinfection was investigated in a murine model. phgp44, which expresses the 44-kDa adhesion/hemagglutinin domain of Arg-gingipain A, preventedP. gingivalis-induced alveolar bone loss. The results indicate that phgp44 could be a candidate antigen for a vaccine againstP. gingivalisinfection.

scholarly journals Existence of natural mouse IgG mAbs recognising epitopes shared by malondialdehyde acetaldehyde adducts and Porphyromonas gingivalis

2021 ◽  
Vol 27 (2) ◽  
pp. 158-169
Author(s):  
Mikael Kyrklund ◽  
Heidi Kaski ◽  
Ramin Akhi ◽  
Antti E Nissinen ◽  
Outi Kummu ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Low Density Lipoprotein ◽  
Physiological Role ◽  
Density Lipoprotein ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
Periodontal Pathogen ◽  
First Line ◽  
Germline Genes ◽  
Innate Recognition

Natural Abs are produced by B lymphocytes in the absence of external Ag stimulation. They recognise self, altered self and foreign Ags, comprising an important first-line defence against invading pathogens and serving as innate recognition receptors for tissue homeostasis. Natural IgG Abs have been found in newborns and uninfected individuals. Yet, their physiological role remains unclear. Previously, no natural IgG Abs to oxidation-specific epitopes have been reported. Here, we show the cloning and characterisation of mouse IgG mAbs against malondialdehyde acetaldehyde (MAA)-modified low-density lipoprotein. Sequence analysis reveals high homology with germline genes, suggesting that they are natural. Further investigation shows that the MAA-specific natural IgG Abs cross-react with the major periodontal pathogen Porphyromonas gingivalis and recognise its principle virulence factors gingipain Kgp and long fimbriae. The study provides evidence that natural IgGs may play an important role in innate immune defence and in regulation of tissue homeostasis by recognising and removing invading pathogens and/or modified self-Ags, thus being involved in the development of periodontitis and atherosclerosis.

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