Comparative virulence of periodontopathogens in a mouse abscess model

Ebersole, J. L.; Kesavaln, L; Schneider, SL; Machen, R. L.; Holt, Stanley C.

doi:10.1111/j.1601-0825.1995.tb00174.x

Cited by 72 publications

(38 citation statements)

References 48 publications

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“…(i) A. actinomycetemcomitans causes extraoral infections, including abscess infections; thus, the model has clinical relevance (17)(18)(19). (ii) The infectious dose is easily controlled and results in a contained infection that has been used to study the pathogenesis of oral bacteria (14,34,35). (iii) Unlike periodontal models of infection, infected tissue can be easily removed to assess disease severity (14) or for RNA isolation.…”

Section: Resultsmentioning

confidence: 99%

Probing Bacterial Metabolism during Infection Using High-Resolution Transcriptomics

et al. 2013

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A fundamental aspect of most infectious diseases is the need for the invading microbe to proliferate in the host. However, little is known about the metabolic pathways required for pathogenic microbes to colonize and persist in their hosts. In this study, we used RNA sequencing (RNA-seq) to generate a high-resolution transcriptome of the opportunistic pathogen Aggregatibacter actinomycetemcomitans in vivo. We identified 691 A. actinomycetemcomitans transcriptional start sites and 210 noncoding RNAs during growth in vivo and as a biofilm in vitro. Compared to in vitro biofilm growth on a defined medium, ϳ14% of the A. actinomycetemcomitans genes were differentially regulated in vivo. A disproportionate number of genes coding for proteins involved in metabolic pathways were differentially regulated in vivo, suggesting that A. actinomycetemcomitans in vivo metabolism is distinct from in vitro growth. Mutational analyses of differentially regulated genes revealed that formate dehydrogenase H and fumarate reductase are important A. actinomycetemcomitans fitness determinants in vivo. These results not only provide a high-resolution genomic analysis of a bacterial pathogen during in vivo growth but also provide new insight into metabolic pathways required for A. actinomycetemcomitans in vivo fitness.

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Section: Resultsmentioning

confidence: 99%

Probing Bacterial Metabolism during Infection Using High-Resolution Transcriptomics

et al. 2013

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“…Thus, it is possible that these two periodontal organisms, which are frequently found together at diseased sites (57), mount a combined operation on fibrinogen that effectively hampers healing processes and promotes bleeding and inflammation. T. denticola has also been detected at other body sites, e.g., atheromatous plaques (8), and may be disseminated to other organs via the vasculature (18,39). In these environments, the ability to interact with fibrinogen may be vital in protection against host-mediated killing.…”

Section: Discussionmentioning

confidence: 99%

The Chymotrypsin-Like Protease Complex ofTreponema denticolaATCC 35405 Mediates Fibrinogen Adherence and Degradation

et al. 2007

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Treponema denticola is an anaerobic spirochete strongly associated with human periodontal disease. T. denticola bacteria interact with a range of host tissue proteins, including fibronectin, laminin, and fibrinogen. The latter localizes in the extracellular matrix where tissue damage has occurred, and interactions with fibrinogen may play a key role in T. denticola colonization of the damaged sites. T. denticola ATCC 35405 showed saturable binding of fluid-phase fibrinogen to the cell surface and saturable adherence to immobilized fibrinogen. Levels of fibrinogen binding were enhanced in the presence of the serine protease inhibitor phenylmethylsulfonyl fluoride. The A␣ and B␤ chains of fibrinogen, but not the ␥ chains, were specifically recognized by T. denticola. Following fibrinogen affinity chromatography analysis of cell surface extracts, a major fibrinogen-binding component (polypeptide molecular mass, ϳ100 kDa), which also degraded fibrinogen, was purified. Upon heating at 100°C, the polypeptide was dissociated into three components (apparent molecular masses, 80, 48, and 45 kDa) that did not individually bind or degrade fibrinogen. The native 100-kDa polypeptide complex was identified as chymotrypsin-like protease (CTLP), or dentilisin. In an isogenic CTLP ؊ mutant strain, CKE, chymotrypsin-like activity was reduced >90% compared to that in the wild type and fibrinogen binding and hydrolysis were ablated. Isogenic mutant strain MHE, deficient in the production of Msp (major surface protein), showed levels of CTLP reduced 40% relative to those in the wild type and exhibited correspondingly reduced levels of fibrinogen binding and proteolysis. Thrombin clotting times in the presence of wild-type T. denticola cells, but not strain CKE (CTLP ؊ ) cells, were extended. These results suggest that interactions of T. denticola with fibrinogen, which may promote colonization and modulate hemostasis, are mediated principally by CTLP.

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“…P. gingivalis, an anaerobic Gram-negative member of the Cytophaga-Bacteroidetes family, belongs to a "red complex" of species associated with chronic periodontal infections (25,43,50). P. gingivalis is a highly heterologous species, and both the most virulent and the least virulent strains have been identified using clinical, animal, and in vitro studies (3,4,15,16,24,36,37,48). It is equipped with multiple virulence factors, including fimbriae, proteases, outer membrane proteins, lipopolysaccharides (LPS), and a capsule.…”

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The Capsule of Porphyromonas gingivalis Leads to a Reduction in the Host Inflammatory Response, Evasion of Phagocytosis, and Increase in Virulence

et al. 2011

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Periodontal disease is a chronic oral inflammatory disease that is triggered by bacteria such as Porphyromonas gingivalis. P. gingivalis strains exhibit great heterogeneity, with some strains being encapsulated while others are nonencapsulated. Although the encapsulated strains have been shown to be more virulent in a mouse abscess model, so far the role of the capsule in P. gingivalis interactions with host cells is not well understood and its role in virulence has not been defined. Here, we investigated the contribution of the capsule to triggering a host response following microbial infection, as well as its protective role following bacterial internalization by host phagocytic cells with subsequent killing, using the encapsulated P. gingivalis strain W50 and its isogenic nonencapsulated mutant, PgC. Our study shows significant time-dependent upregulation of the expression of various groups of genes in macrophages challenged with both the encapsulated and nonencapsulated P. gingivalis strains. However, cells infected with the nonencapsulated strain showed significantly higher upregulation of 9 and 29 genes at 1 h and 8 h postinfection, respectively, than cells infected with the encapsulated strain. Among the genes highly upregulated by the nonencapsulated PgC strain were ones coding for cytokines and chemokines. Maturation markers were induced at a 2-fold higher rate in dendritic cells challenged with the nonencapsulated strain for 4 h than in dendritic cells challenged with the encapsulated strain. The rates of phagocytosis of the nonencapsulated P. gingivalis strain by both macrophages and dendritic cells were 4.5-fold and 7-fold higher, respectively, than the rates of phagocytosis of the encapsulated strain. On the contrary, the survival of the nonencapsulated P. gingivalis strain was drastically reduced compared to the survival of the encapsulated strain. Finally, the encapsulated strain exhibited greater virulence in a mouse abscess model. Our results indicate that the P. gingivalis capsule plays an important role in aiding evasion of host immune system activation, promoting survival of the bacterium within host cells, and increasing virulence. As such, it is a major virulence determinant of P. gingivalis.

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Comparative virulence of periodontopathogens in a mouse abscess model

Cited by 72 publications

References 48 publications

Probing Bacterial Metabolism during Infection Using High-Resolution Transcriptomics

Probing Bacterial Metabolism during Infection Using High-Resolution Transcriptomics

The Chymotrypsin-Like Protease Complex ofTreponema denticolaATCC 35405 Mediates Fibrinogen Adherence and Degradation

The Capsule of Porphyromonas gingivalis Leads to a Reduction in the Host Inflammatory Response, Evasion of Phagocytosis, and Increase in Virulence

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