Virulence of six capsular serotypes of Porphyromonas gingivalis in a mouse model.
TL;DR: Differences in virulence within a capsular serotype suggest that the capsule is an important but not the only determining virulence factor for P. gingivalis.
Abstract: Capsular structures of Porphyromonas gingivalis have been correlated to the pathogenicity in animal models. Six polysaccharide capsular serotypes have recently been described in P. gingivalis. In the present study, virulence of the P. gingivalis strains of the six capsular serotypes was compared with strains of the non-capsular serotype of P. gingivalis in a mouse model. All 18 encapsulated strains caused a spreading type of infection with exudate, often accompanied by ulceration and necrosis of the skin and a significant loss of body weight. All three non-encapsulated strains tested induced localized abscesses, although a spreading type of infection was occasionally observed. Illness of the mice was almost always associated with recovery of encapsulated P. gingivalis from blood, kidneys, lungs and spleens. A statistically significant contrast was found in the average weight change during the experiment between the mice infected with the K- serotype strains and the mice infected with the encapsulated P. gingivalis strains. Differences in severity of illness and the recovery of P. gingivalis from mouse tissues were recorded between strains of the same serotype. The differences in virulence within a capsular serotype suggest that the capsule is an important but not the only determining virulence factor for P. gingivalis.
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TL;DR: The present review discusses the invasive and evasive strategies of P. gingivalis and the role of its major virulence factors in these, namely lipopolysaccharide, capsule, gingipains and fimbriae.
Abstract: Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis, an inflammatory disease that destroys the tissues supporting the tooth, eventually leading to tooth loss. Porphyromonas gingivalis has can locally invade periodontal tissues and evade the host defence mechanisms. In doing so, it utilizes a panel of virulence factors that cause deregulation of the innate immune and inflammatory responses. The present review discusses the invasive and evasive strategies of P. gingivalis and the role of its major virulence factors in these, namely lipopolysaccharide, capsule, gingipains and fimbriae. Moreover, the role of P. gingivalis as a 'keystone' biofilm species in orchestrating a host response, is highlighted.
420 citations
TL;DR: The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined and confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria.
Abstract: The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined. Whole-genome comparative analysis with other available complete genome sequences confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria. Within the CFB phyla, the genomes most similar to that of P. gingivalis are those of Bacteroides thetaiotaomicron and B. fragilis. Outside of the CFB phyla the most similar genome to P. gingivalis is that of Chlorobium tepidum, supporting the previous phylogenetic studies that indicated that the Chlorobia and CFB phyla are related, albeit distantly. Genome analysis of strain W83 reveals a range of pathways and virulence determinants that relate to the novel biology of this oral pathogen. Among these determinants are at least six putative hemagglutinin-like genes and 36 previously unidentified peptidases. Genome analysis also reveals that P. gingivalis can metabolize a range of amino acids and generate a number of metabolic end products that are toxic to the human host or human gingival tissue and contribute to the development of periodontal disease.
378 citations
Brown University1, Harvard University2, Imperial College London3, German Cancer Research Center4, Aarhus University5, International Agency for Research on Cancer6, South University7, Institut Gustave Roussy8, National and Kapodistrian University of Athens9, Academy of Athens10, University of Naples Federico II11, Utrecht University12, University of Tromsø13, Andalusian School of Public Health14, Umeå University15, Karolinska Institutet16, University of Gothenburg17, Lund University18, University of Cambridge19, Medical Research Council20, University of Oxford21
TL;DR: Monitoring of antibodies to oral bacteria in prediagnosis blood samples found that increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer.
Abstract: Objective Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.
Design We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index.
Results Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83).
Conclusions Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.
291 citations
TL;DR: Current knowledge on the molecular cross-talk between P. gingivalis andGingival epithelial cells in the development of periodontitis is reviewed.
Abstract: Emerging data on the consequences of the interactions between invasive oral bacteria and host cells have provided new insights into the pathogenesis of periodontal disease. Indeed, modulation of the mucosal epithelial barrier by pathogenic bacteria appears to be a critical step in the initiation and progression of periodontal disease. Periodontopathogens such as Porphyromonas gingivalis have developed different strategies to perturb the structural and functional integrity of the gingival epithelium. P. gingivalis adheres to, invades, and replicates within human epithelial cells. Adhesion of P. gingivalis to host cells is multimodal and involves the interaction of bacterial cell-surface adhesins with receptors expressed on the surfaces of epithelial cells. Internalization of P. gingivalis within host cells is rapid and requires both bacterial contact-dependent components and host-induced signaling pathways. P. gingivalis also subverts host responses to bacterial challenges by inactivating immune cells and molecules and by activating host processes leading to tissue destruction. The adaptive ability of these pathogens that allows them to survive within host cells and degrade periodontal tissue constituents may contribute to the initiation and progression of periodontitis. In this paper, we review current knowledge on the molecular cross-talk between P. gingivalis and gingival epithelial cells in the development of periodontitis.
157 citations
References
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TL;DR: The microbiota of two young adult patients with generalized extensive bone loss, extensive clinical inflammation and suppuration was dominated by Bacteroides asaccharolyticus and an organism with characteristics consistent with Actinobacillus actinomycetemcomitans, while the subgingival microbiota in advanced destructive sites was predominated by Gram-negative rods.
Abstract: Samples of apical plaque were taken by means of an anaerobic gas-flushed syringe from 21 sites in eight patients. The samples were anaerobically dispersed, diluted and plated and incubated in an atmosphere of 80% N2, 10% H2 and 10% CO2 for 7-21 days. All colonies on plates containing 20-50 isolates were picked, repeatedly restreaked, characterized and identified where possible by a probabilistic computer identification program. The sites were divided into four groups on the basis of clinical features. The significance of differences between bacterial populations in the groups was determined by the Kruskal Wallis and Mann-Whitney U tests, while the Spearman rank correlation coefficient was used to determine the rank correlation of clinical features of diseases and microbial species. The subgingival microbiota in advanced destructive sites was predominated by Gram-negative rods. The microbiota of two young adult patients with generalized extensive bone loss, extensive clinical inflammation and suppuration was dominated by Bacteroides asaccharolyticus and an organism with characteristics consistent with Actinobacillus actinomycetemcomitans. The predominant cultivable microbiota in two patients with extensive bone loss but minimal clinical inflammation was predominated by Bacteroides melaninogenicus ss intermedius and Eikenella corrodens in one patient and E. corrodens and a slow growing fusiform-shaped Bacteroides in a second patient. A third group of four patients demonstrated moderate levels of clinical inflammation and evidence of continued bone loss in the last year. Predominant organisms in this group were more heterogeneous and included B. asaccharolyticus, Fusobacterium nucleatum, the "fusiform" Bacteroides and anaerobic vibrios. Sites with minimal disease in the patients revealed higher proportions of Gram-positive organisms including Rothia dentocariosa, Actinomyces naeslundii and Actinomyces viscosus. A positive rank correlation could be detected between clinical inflammation including suppuration and B. asaccharolyticus and a negative rank correlation between inflammation and E. corrodens.
915 citations
TL;DR: Black-pigmented Bacteroides gingivalis is by far the most proteolytic species, followed by B. endodontalis, which seems to be the most pathogenic and virulent species.
Abstract: Today, 10 black-pigmented Bacteroides (BPB) species are recognized The majority of these species can be isolated from the oral cavity BPB species are involved in anaerobic infections of oral and non-oral sites In the oral cavity, BPB species are associated with gingivitis, periodontitis, endodontal infections and odontogenic abscesses Cultural studies suggest a specific role of the various BPB species in the different types of infection Bacteroides gingivalis is closely correlated with destructive periodontitis in adults as well as in juveniles Bacteroides intermedius seems to be less specific since it is found in gingivitis, periodontitis, endodontal infections and odontogenic abscesses The recently described Bacteroides endodontalis is closely associated with endodontal infections and odontogenic abscesses of endodontal origin There are indications that these periodontopathic BPB species are only present in the oral cavity of subjects suffering from periodontal breakdown, being absent on the mucosal surfaces of subjects without periodontal breakdown BPB species associated with healthy oral conditions are Bacteroides melaninogenicus, Bacteroides denticola and Bacteroides loescheii There are indications that these BPB species are part of the normal indigenous oral microflora Many studies in the past have documented the pathogenic potential and virulence of BPB species This virulence can be explained by the large numbers of virulence factors demonstrated in this group of micro-organisms Among others, the proteolytic activity seems to be one of the most important features Several artificial substrates as well as numerous biological proteins are degraded These include anti-inflammatory proteins such as alpha-2-macroglobulin, alpha-1-antitrypsin, C3 and C5 complement factors and immunoglobulins B gingivalis is by far the most proteolytic species, followed by B endodontalis Like other bacteria, the lipopolysaccharide of B gingivalis has shown to be active in bone resorption in vitro and is capable in stimulating interleukin-1 production in human peripheral monocytes Based on the well documented association with periodontal disease and the possession of relevant virulence factors, BPB species must be considered as important micro-organisms in the etiology of oral infections B gingivalis seems to be the most pathogenic and virulent species
290 citations
TL;DR: In comparison with untreated patients, unsuccessfully treated patients solely infected with A. actinomycetemcomitans had on average a lower number but also a higher mean % of this bacterium than in patients who were also infected with black-pigmented Bacteroides species.
Abstract: A total of 242 subjects including 138 untreated severe periodontitis patients and 104 patients with refractory periodontal disease, previously treated for severe periodontitis, were examined for the occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius Pooled subgingival samples of representative periodontal lesions were used for anaerobic cultivation on blood agar and for the enumeration of A actinomycetemcomitans on selective TSBV medium 97% of the untreated patients were infected with one or more of the test micro-organisms In this patient group, the occurrence of A actinomycetemcomitans, B gingivalis and B intermedius was 54%, 48% and 63%, respectively The prevalence of A actinomycetemcomitans positive patients appeared to be age related and decreased with increasing age Likewise, the number of patients solely infected with A actinomycetemcomitans decreased with increasing age The prevalence of B gingivalis infected patients appeared to increase with increasing age These phenomena were not observed in the refractory periodontitis patients The occurrence of A actinomycetemcomitans, B gingivalis and B intermedius in the refractory periodontitis group was 55%, 27% and 59%, respectively A statistical significant difference in the prevalence of B gingivalis was found between the untreated and the refractory periodontitis patients In both patient groups, the relative proportion of A actinomycetemcomitans was significantly higher in subjects with this bacterium as the sole indicator micro-organism than in patients who, besides being infected with A actinomycetemcomitans, were also infected with black-pigmented Bacteroides species Furthermore, in comparison with untreated patients, unsuccessfully treated patients solely infected with A actinomycetemcomitans had on average a lower number but also a higher mean % of this bacterium(ABSTRACT TRUNCATED AT 250 WORDS)
200 citations
TL;DR: Strains of Bacteroides gingivalis were compared for the presence of properties associated with pathogenicity and some strains were infectious in pure culture in an in vivo model (guinea pig), and all but one of these were more collagenolytic than those which failed to cause lesions in guinea pigs.
Abstract: Strains of Bacteroides gingivalis were compared for the presence of properties associated with pathogenicity. Some strains were infectious in pure culture in an in vivo model (guinea pig), and all but one of these were more collagenolytic than those which failed to cause lesions in guinea pigs. However, other factors seem to be necessary for the induction of an infection in this animal model.
194 citations
TL;DR: The ability of fresh isolates of B. gingivalis to establish abscesses in the mouse model was studied by comparing them with established laboratory strains, and four synthetic enzyme substrates were examined to determine whether the differences between invasive and non-invasive strains were due to differences in proteolytic enzyme production.
Abstract: The ability of fresh isolates of B. gingivalis to establish abscesses in the mouse model was studied by comparing them with established laboratory strains of B. gingivalis. Eight fresh isolates obtained from plaque associated with periodontal disease and grown under similar conditions as established strains were injected subcutaneously on the back of the mouse. All of these strains produced secondary lesions on the abdomen. Septicemia was associated with seven of the strains. Two commonly used laboratory strains, W50 and W83, also produced secondary lesions and septicemia. Five other laboratory strains produced only localized abscesses. On histologic examination, the strains that produced disseminated disease showed invasion of connective disease by individual bacteria that were not in clumps. The strains that produced localized abscesses were characterized by growing in colonies or clumps in the abscess cavity. Four synthetic enzyme substrates were examined to determine whether the differences between invasive and non-invasive strains were due to differences in proteolytic enzyme production. No differences in enzyme production could be demonstrated with the selected substrates.
194 citations