Virulence Mechanisms of Leukotoxin from Aggregatibacter actinomycetemcomitans

Context and Objective:Statin treatment, apart from its hypolipidemic action has proven its antimicrobial activity by improving the survival rate of patients with severe systemic bacterial infections. Periodontitis is an inflammatory disorder of tooth supporting structures caused by a group of specific microorganisms. The objective of the present study was to determine the antimicrobial activity of pure simvastatin drug against the primary periodontal pathogens.Materials and Methods:Minimum inhibitory concentration (MIC) was determined against Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans using serial dilution method.Results:MIC of simvastatin against P. gingivalis was 2 μg/ml and A. actinomycetemcomitans was found to be <1 μg/ml which requires further dilutions to determine the exact value.Conclusions:Data suggests a potent antimicrobial activity of simvastatin against both A. actinomycetemcomitans and P gingivalis. Hence simvastatin can be prescribed as a dual action drug in patients with both hyperlipidemia and periodontal disease.

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“…A. actinomycetemcomitans secretes leukotoxin, which was suggested to be in association between periodontitis and CVD. [ 25 ]…”

Section: Discussionmentioning

confidence: 99%

Determination of the antibacterial activity of simvastatin against periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: An in vitro study

2014

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“…Interaction between hDFSCs and A. actinomycetemcomitans reduced the number of viable neutrophils, a phenotype that could depend on the secretion of a leukotoxin. Leukotoxins activate neutrophils and lead to the release of proteolytic enzymes [34]. The infection of hDFSCs with P. intermedia and T. forsythia had no influence on neutrophil apoptosis.…”

Section: Discussionmentioning

confidence: 99%

<b><i>Porphyromonas gingivalis</i></b> Peptidyl Arginine Deiminase Can Modulate Neutrophil Activity via Infection of Human Dental Stem Cells

et al. 2018

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Periodontitis (PD) is a widespread chronic inflammatory disease in the human population. Porphyromonas gingivalis is associated with PD and can citrullinate host proteins via P. gingivalis peptidyl arginine deiminase (PPAD). Here, we hypothesized that infection of human dental follicle stem cells (hDFSCs) with P. gingivalis and subsequent interaction with neutrophils will alter the neutrophil phenotype. To test this hypothesis, we established and analyzed a triple-culture system of neutrophils and hDFSCs primed with P. gingivalis. Mitogen-activated pathway blocking reagents were applied to gain insight into stem cell signaling after infection. Naïve hDFSCs do not influence the neutrophil phenotype. However, infection of hDFSCs with P. gingivalis prolongs the survival of neutrophils and increases their migration. These phenotypic changes depend on direct cellular contacts and PPAD expression by P. gingivalis. Active JNK and ERK pathways in primed hDFSCs are essential for the phenotypic changes in neutrophils. Collectively, our results confirm that P. gingivalis modifies hDFSCs, thereby causing an immune imbalance.

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“…This pro-inflammatory cytokine is a key molecule that regulates the balance between catabolic and anabolic processes in tissue homeostasis, and therefore is of specific interest for tissue degenerative diseases, such as periodontitis (modified from Ref. 177 ).…”

Section: Leukotoxinmentioning

confidence: 99%

“…This results in the release of biologically active molecules with a capacity to cause an imbalance of the host response that can promote degenerative processes in the tooth-supporting tissues (modified from Ref. 177 ).…”

Section: Leukotoxinmentioning

confidence: 99%

Pathogenicity of the highly leukotoxic JP2 clone ofAggregatibacter actinomycetemcomitansand its geographic dissemination and role in aggressive periodontitis

Haubek

Johansson

2014

Journal of Oral Microbiology

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For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2 clone, are likely to share this clone with several family members because the clone is transmitted through close contacts. This is a challenge to the clinicians. The patients need intense monitoring of their periodontal status as the risk for developing severely progressing periodontal lesions are relatively high. Furthermore, timely periodontal treatment, in some cases including periodontal surgery supplemented by the use of antibiotics, is warranted. Preferably, periodontal attachment loss should be prevented by early detection of the JP2 clone of A. actinomycetemcomitans by microbial diagnostic testing and/or by preventive means.

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Virulence Mechanisms of Leukotoxin from Aggregatibacter actinomycetemcomitans

Cited by 5 publications

References 115 publications

Determination of the antibacterial activity of simvastatin against periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: An in vitro study

Determination of the antibacterial activity of simvastatin against periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: An in vitro study

<b><i>Porphyromonas gingivalis</i></b> Peptidyl Arginine Deiminase Can Modulate Neutrophil Activity via Infection of Human Dental Stem Cells

Pathogenicity of the highly leukotoxic JP2 clone ofAggregatibacter actinomycetemcomitansand its geographic dissemination and role in aggressive periodontitis

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