Leukotoxic activity of Aggregatibacter actinomycetemcomitans and periodontal attachment loss.

Carola Höglund Åberg,Dorte Haubek,Rolf Claesson,Anders Johansson,Francis Kwamin,Michael Glogauer

doi:10.1371/journal.pone.0104095

Carola Höglund Åberg, Dorte Haubek + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0104095

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Journal: PloS one	Publication Date: Aug 5, 2014
Citations: 99	License type: CC BY 4.0

Affiliation: Umeå University, Aarhus University, University of Ghana

Abstract

Aggregatibacter actinomycetemcomitans is a Gram-negative periodontitis-associated bacterium that expresses a toxin that selectively affects leukocytes. This leukotoxin is encoded by an operon belonging to the core genome of this bacterial species. Variations in the expression of the leukotoxin have been reported, and a well-characterized specific clonal type (JP2) of this bacterium with enhanced leukotoxin expression has been isolated. In particular, the presence of the JP2 genotype significantly increases the risk for the progression of periodontal attachment loss (AL). Based on these findings we hypothesized that variations in the leukotoxicity are linked to disease progression in infected individuals. In the present study, the leukotoxicity of 239 clinical isolates of A. actinomycetemcomitans was analysed with different bioassays, and the genetic peculiarities of the isolates were related to their leukotoxicity based on examination with molecular techniques. The periodontal status of the individuals sampled for the presence of A. actinomycetemcomitans was examined longitudinally, and the importance of the observed variations in leukotoxicity was evaluated in relation to disease progression. Our data show that high leukotoxicity correlates with an enhanced risk for the progression of AL. The JP2 genotype isolates were all highly leukotoxic, while the isolates with an intact leukotoxin promoter (non-JP2 genotypes) showed substantial variation in leukotoxicity. Genetic characterization of the non-JP2 genotype isolates indicated the presence of highly leukotoxic genotypes of serotype b with similarities to the JP2 genotype. Based on these results, we conclude that A. actinomycetemcomitans harbours other highly virulent genotypes besides the previously described JP2 genotype. In addition, the results from the present study further highlight the importance of the leukotoxin as a key virulence factor in aggressive forms of periodontitis.

Highlights

Periodontitis is an inflammatory disease, initiated by a bacterial biofilm on the teeth and characterized by the degradation of the tooth-supporting tissues [1]
We tested if haemolysis that is induced when A. actinomycetemcomitans is grown on blood agar can be used as a leukotoxin assay [12]
In the present study we have shown that individuals harbouring highly leukotoxic A. actinomycetemcomitans, independently of carrying a complete or truncated (JP2-genotype) leukotoxin promoter, had a significantly increased risk of progression of attachment loss (AL)

Summary

Introduction

Periodontitis is an inflammatory disease, initiated by a bacterial biofilm on the teeth and characterized by the degradation of the tooth-supporting tissues [1]. The presence of A. actinomycetemcomitans is considered a risk marker for the progression of periodontal attachment loss (AL), i.e. degradation of the periodontal tissues around the teeth [3,4,5]. While a cytolethal distending toxin (CDT) produced by this bacterial species seems to have limited effect on disease progression, the opposite has been reported for the leukotoxin, another toxin produced by the bacterium [6]. A specific genotype of A. actinomycetemcomitans, JP2, with the capacity to produce substantial amounts of the leukotoxin, has been shown to be highly associated with aggressive forms of periodontitis [5,7]

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Results

Conclusion