Oxantel Disrupts Polymicrobial Biofilm Development of Periodontal Pathogens
ABSTRACT Bacterial pathogens commonly associated with chronic periodontitis are the spirochaete Treponema denticola and the Gram-negative, proteolytic, species Porphyromonas gingivalis and Tannerella forsythia. These species rely on complex anaerobic respiration of amino acids and the anthelmintic drug Oxantel has been shown to inhibit fumarate reductase (Frd) activity in some pathogenic bacteria and inhibit P. gingivalis homotypic biofilm formation. Here we demonstrate that Oxantel inhibited P. gingivalis Frd activity with an IC50 of 2.2 μM and planktonic growth of T. forsythia with a minimal inhibitory concentration of 295 μM, but had no effect on the growth of T. denticola. Oxantel treatment caused the downregulation of six P. gingivalis gene products and the upregulation of 22 gene products. All of these genes are part of a regulon controlled by haem availability. There was no large scale change in the expression of genes encoding metabolic enzymes indicating that P. gingivalis may be unable to overcome Frd inhibition. Oxantel disrupted the development of polymicrobial biofilms composed of P. gingivalis, T. forsythia and T. denticola in a concentration dependent manner. In these biofilms all three species were inhibited to a similar degree demonstrating the synergistic nature of biofilm formation by these species and the dependence of T. denticola on the other two species. In a murine alveolar bone loss model of periodontitis Oxantel addition to the drinking water of P. gingivalis-infected mice reduced bone loss to the same level as the uninfected control.
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ABSTRACT: To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions.PLoS ONE 06/2014; 9(6):e100838. DOI:10.1371/journal.pone.0100838 · 3.53 Impact Factor