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Pathologie-biologie 2007Periodontitis are mixed bacterial infections leading to destruction of tooth-supporting tissues, including periodontal ligament and alveolar bone. Among over 500... (Review)
Review
Periodontitis are mixed bacterial infections leading to destruction of tooth-supporting tissues, including periodontal ligament and alveolar bone. Among over 500 bacterial species living in the oral cavity, a bacterial complex named "red complex" and made of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia has been strongly related to advanced periodontal lesions. While periodontopathogenic bacteria are the primary etiologic factor of periodontitis, tissue destruction essentially results from the host immune response to the bacterial challenge. Members of the red complex are Gram negative anaerobic bacteria expressing numerous virulence factors allowing bacteria to colonize the subgingival sites, to disturb the host defense system, to invade and destroy periodontal tissue as well as to promote the immunodestructive host response. This article reviews current knowledge of the pathogenic mechanisms of bacteria of the red complex leading to tissue and alveolar bone destruction observed during periodontitis.
Topics: Animals; Apoptosis; Bacteroidaceae Infections; Disease Models, Animal; Humans; Nutritional Status; Peptide Hydrolases; Periodontal Pocket; Periodontitis; Porphyromonas; Porphyromonas gingivalis; Treponema denticola
PubMed: 17049750
DOI: 10.1016/j.patbio.2006.07.045 -
PloS One 2017Porphyromonas gingivalis, a periodontopathic gram-negative anaerobic bacterium, generally expresses two types of fimbriae, FimA and Mfa1. However, a novel potential...
Porphyromonas gingivalis, a periodontopathic gram-negative anaerobic bacterium, generally expresses two types of fimbriae, FimA and Mfa1. However, a novel potential fimbrilin, PGN_1808, in P. gingivalis strain ATCC 33277 was recently identified by an in silico structural homology search. In this study, we experimentally examined whether the protein formed a fimbrial structure. Anion-exchange chromatography showed that the elution peak of the protein was not identical to those of the major fimbrilins of FimA and Mfa1, indicating that PGN_1808 is not a component of these fimbriae. Electrophoretic analyses showed that PGN_1808 formed a polymer, although it was detergent and heat labile compared to FimA and Mfa1. Transmission electron microscopy showed filamentous structures (2‒3 nm × 200‒400 nm) on the cell surfaces of a PGN_1808-overexpressing P. gingivalis mutant (deficient in both FimA and Mfa1 fimbriae) and in the PGN_1808 fraction. PGN_1808 was detected in 81 of 84 wild-type strains of P. gingivalis by western blotting, suggesting that the protein is generally present in P. gingivalis.
Topics: Amino Acid Sequence; Bacterial Proteins; Chromatography, Gel; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Fimbriae Proteins; Mass Spectrometry; Microscopy, Electron, Transmission; Models, Molecular; Porphyromonas gingivalis; Protein Conformation
PubMed: 28296909
DOI: 10.1371/journal.pone.0173541 -
The Tohoku Journal of Experimental... Sep 2015Porphyromonas strains, including Porphyromonas-like strains, have been isolated from oral and various other systemic infections. The characterization of such strains is...
Porphyromonas strains, including Porphyromonas-like strains, have been isolated from oral and various other systemic infections. The characterization of such strains is a crucial issue, because such information contributes to both the taxonomy of anaerobic bacteria and the clinical aspects of infectious diseases. We previously isolated four Porphyromonas-like strains from intraoperative bronchial fluids of a patient with non-small cell lung cancer. This study aimed to characterize the genetic, biochemical and chemotaxonomic aspects of these isolates. Each strain only grew under anaerobic conditions and their colony morphology was convex, 0.1-1.0 mm in diameter, light gray, and slightly glistening colony, with no black or brown pigmentation on blood agar plates after five-day incubation. The pigmentation was helpful to differentiate the isolates from other Porphyromonas, as most of Porphyromonas species show the pigmentation. In the 16S rRNA gene phylogenetic analysis (98% sequence identity of isolates indicates the same species), the four isolates were closely related to one another (99.7-100.0%), but not related to Porphyromonas (P.) catoniae, the closest species (96.9%). In addition, the DNA-DNA hybridization data revealed less than 16% similarity values between a representative isolate and the P. catoniae, indicating that the strains were genetically independent. Biochemically, the isolates could be differentiated from closely related species, i.e., P. catoniae, P. gingivalis, P. gulae, and P. pogonae, with trypsin activity (negative only in the isolates) and leucine arylamidase activity (positive only in the isolates). We therefore propose a new species to include these isolates: Porphyromonas bronchialis sp. nov.
Topics: Aged; Body Fluids; Bronchi; Carcinoma, Non-Small-Cell Lung; DNA, Bacterial; Fatty Acids; Fermentation; Humans; Intraoperative Period; Lung Neoplasms; Male; Porphyromonas; RNA, Ribosomal, 16S; Species Specificity; Trypsin
PubMed: 26320571
DOI: 10.1620/tjem.237.31 -
International Journal of Systematic and... Jul 2009During our investigation of the bacteriology of human wound infections and abscesses, a novel anaerobic, non-spore-forming, Gram-negative bacillus was frequently...
During our investigation of the bacteriology of human wound infections and abscesses, a novel anaerobic, non-spore-forming, Gram-negative bacillus was frequently isolated. On the basis of morphological and biochemical criteria, the strains were tentatively identified as belonging to the family Bacteroidaceae, but they did not appear to correspond to any recognized species of this family. Comparative 16S rRNA gene sequencing showed that the 14 novel strains were genotypically homogeneous and confirmed their placement in the genus Porphyromonas. Sequence divergence values >10 % with respect to reference Porphyromonas species demonstrated that the strains isolated represent a novel species. On the basis of biochemical criteria and phylogenetic considerations, it is proposed that these strains isolated from human sources should be assigned to a novel species of the genus Porphyromonas, named Porphyromonas bennonis sp. nov., with WAL 1926C(T) (=ATCC BAA-1629(T) =CCUG 55979(T)) as the type strain.
Topics: Bacterial Typing Techniques; Bacteroidaceae Infections; DNA, Bacterial; Genes, rRNA; Genotype; Humans; Molecular Sequence Data; Phenotype; Phylogeny; Porphyromonas; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Species Specificity
PubMed: 19542133
DOI: 10.1099/ijs.0.001909-0 -
International Journal of Systematic... Apr 1994A new species, Porphyromonas canoris, is proposed for black-pigmented asaccharolytic strains isolated from subgingival plaque samples from dogs with naturally occurring... (Comparative Study)
Comparative Study
A new species, Porphyromonas canoris, is proposed for black-pigmented asaccharolytic strains isolated from subgingival plaque samples from dogs with naturally occurring periodontal disease. This bacterium is an obligately anaerobic, nonmotile, non-spore-forming, gram-negative, rod-shaped organism. On laked rabbit blood or sheep blood agar plates, colonies are light brown to greenish brown after 2 to 4 days of incubation and dark brown after 14 days of incubation. Colonies on egg yolk agar and on nonhemolyzed sheep blood agar are orange. The cells do not grow in the presence of 20% bile and have a guanine-plus-cytosine content of 49 to 51 mol%. The type strain is VPB 4878 (= NCTC 12835). The average levels of DNA-DNA hybridization between P. canoris strains and other members of the genus Porphyromonas are as follows: Porphyromonas gingivalis ATCC 33277T (T = type strain), 6.5%; Porphyromonas gingivalis cat strain VPB 3492, 5%; Porphyromonas endodontalis ATCC 35406T, 1%; Porphyromonas salivosa NCTC 11362T, 5%; and Porphyromonas circumdentaria NCTC 12469T, 6%. The level of hybridization between P. canoris NCTC 12835T DNA and Porphyromonas asaccharolytica ATCC 25260T DNA is 3%. P. canoris cells produce major amounts of acetic, propionic, isovaleric, and succinic acids and minor amounts of isobutyric and butyric acids as end products of metabolism in cooked meat medium. The major cellular fatty acid is 13-methyltetradecanoic acid (iso-C15:0). Glutamate and malate dehydrogenases are present, as are glucose-6-phosphate dehydrogenase activity (65.7 nmol mg of protein-1 min-1) and 6-phosphogluconate dehydrogenase activity (63.0 nmol mg of protein-1 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Bacterial Typing Techniques; Carbohydrate Metabolism; DNA, Bacterial; Dental Plaque; Dogs; Fatty Acids; Gingiva; Gingival Diseases; Nucleic Acid Hybridization; Pigments, Biological; Porphyromonas
PubMed: 8186085
DOI: 10.1099/00207713-44-2-204 -
Advances in Dental Research Feb 1995As with other pathogens, a requirement for the in vivo growth of Porphyromonas gingivalis is that the organism must be capable of obtaining iron from the host. The... (Review)
Review
As with other pathogens, a requirement for the in vivo growth of Porphyromonas gingivalis is that the organism must be capable of obtaining iron from the host. The ability to utilize hemin and hemin-containing compounds for nutritional iron has been documented for several pathogenic bacteria, including P. gingivalis; however, the mechanisms involved in hemin uptake are poorly defined. I have determined that P. gingivalis transports the entire hemin moiety into the cell by an energy-dependent mechanism and that the binding and accumulation of hemin are induced by growth of cultures in the presence of hemin. A model of hemin transport in P. gingivalis consistent with these results is presented. I have also found that, in P. gingivalis, hemin regulates the expression of several putative virulence factors; this in turn results in the increased virulence potential of P. gingivalis as assessed in an animal model. Regulation of hemin-responsive genes in P. gingivalis may occur by a negative regulator, as has been described in other pathogenic organisms.
Topics: Bacterial Outer Membrane Proteins; Base Sequence; Biological Transport, Active; DNA Primers; Gene Expression Regulation, Bacterial; Genes, Bacterial; Hemin; Iron; Molecular Sequence Data; Porphyromonas gingivalis; Virulence
PubMed: 7669213
DOI: 10.1177/08959374950090010801 -
Pharmacology Research & Perspectives Feb 2020COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory...
COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans.
Topics: Administration, Oral; Aging; Animals; Bacterial Load; Bacterial Proteins; Bacteroidaceae Infections; Brain; Dog Diseases; Dogs; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Gingipain Cysteine Endopeptidases; Gingival Crevicular Fluid; Organic Chemicals; Periodontal Diseases; Porphyromonas; Saliva; Small Molecule Libraries
PubMed: 31999052
DOI: 10.1002/prp2.562 -
Infection and Immunity Apr 2019Although the periodontal pathogen must withstand high levels of nitrosative stress while in the oral cavity, the mechanisms of nitrosative stress defense are not well...
Although the periodontal pathogen must withstand high levels of nitrosative stress while in the oral cavity, the mechanisms of nitrosative stress defense are not well understood in this organism. Previously we showed that the transcriptional regulator HcpR plays a significant role in defense, and here we further defined its regulon. Our study shows that (PG0893), a putative nitric oxide (NO) reductase, is the only gene significantly upregulated in response to nitrite (NO) and that this regulation is dependent on HcpR. An isogenic mutant deficient in is not able to grow with 200 μM nitrite, demonstrating that the sensitivity of the HcpR mutant is mediated through Hcp. We further define the molecular mechanisms of HcpR interaction with the promoter through mutational analysis of the inverted repeat present within the promoter. Although other putative nitrosative stress protection mechanisms present on the operon are also found in the genome, we show that their gene products play no role in growth of the bacterium with nitrite. As growth of the -deficient strain was also significantly diminished in the presence of a nitric oxide-producing compound, -nitrosoglutathione (GSNO), Hcp appears to be the primary means by which responds to NO-based stress. Finally, we show that Hcp is required for survival with host cells but that loss of Hcp has no effect on association and entry of into human oral keratinocytes.
Topics: Bacterial Proteins; Bacteroidaceae Infections; Gene Expression Regulation, Bacterial; Humans; Microbial Viability; Nitrites; Operon; Oxidoreductases; Porphyromonas gingivalis
PubMed: 30670550
DOI: 10.1128/IAI.00572-18 -
JCI Insight Oct 2022
Topics: Animals; Porphyromonas gingivalis; Arthritis, Experimental
PubMed: 36278492
DOI: 10.1172/jci.insight.165600 -
Biofouling Feb 2021biofilms are implicated in the pathology of peri-implantitis and periodontitis. In this study, D-arginine (R), D-methionine (M), D-histidine (H), and a mixture of these...
biofilms are implicated in the pathology of peri-implantitis and periodontitis. In this study, D-arginine (R), D-methionine (M), D-histidine (H), and a mixture of these D-amino acids (D-AAs) were investigated as an effective therapeutic strategy against biofilms. The bacterial growth activity and minimum inhibitory concentrations were determined for each D-AA, along with the effects of the D-AAs mixture on biofilm development, morphology, structure, extracellular polysaccharides (EPS), cytotoxicity towards commensals, and bacterial structure. The D-AA mixture delayed the proliferation of , changed its membrane structure, and decreased biofilm thickness and integrity, as compared with individual D-AAs. The EPS content increased with the concentration of D-AAs. The present study shows that a 4 mM RMH, triple D-AA mixture, enhanced deleterious effects on biofilms without any cytotoxicity compared with individual D-AAs, thus providing a new strategy for the treatment of peri-implantitis and periodontitis.
Topics: Arginine; Biofilms; Histidine; Methionine; Porphyromonas gingivalis
PubMed: 33682548
DOI: 10.1080/08927014.2021.1893309