Abstract

BackgroundStreptococcus mutans is a major pathogen in human dental caries. One of its important virulence properties is the ability to form biofilms (dental plaque) on tooth surfaces. Eradication of such biofilms is extremely difficult. We therefore screened a library of secondary metabolites from myxobacteria for their ability to damage biofilms of S. mutans.ResultsHere we show that carolacton, a secondary metabolite isolated from Sorangium cellulosum, has high antibacterial activity against biofilms of S. mutans. Planktonic growth of bacteria was only slightly impaired and no acute cytotoxicity against mouse fibroblasts could be observed. Carolacton caused death of S. mutans biofilm cells, elongation of cell chains, and changes in cell morphology. At a concentration of 10 nM carolacton, biofilm damage was already at 35% under anaerobic conditions. A knock-out mutant for comD, encoding a histidine kinase specific for the competence stimulating peptide (CSP), was slightly less sensitive to carolacton than the wildtype. Expression of the competence related alternate sigma factor ComX was strongly reduced by carolacton, as determined by a pcomX luciferase reporter strain.ConclusionsCarolacton possibly interferes with the density dependent signalling systems in S. mutans and may represent a novel approach for the prevention of dental caries.

Highlights

  • Streptococcus mutans is a major pathogen in human dental caries

  • Dental caries and periodontal diseases, which are among the most common bacterial infections in humans, are caused by biofilms known as dental plaque that result from microbial colonization of the tooth surface or the subgingival margin [6,7]

  • We focused in our search for biofilm inhibitors on our collection of secondary metabolites from myxobacteria

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Summary

Introduction

Streptococcus mutans is a major pathogen in human dental caries. One of its important virulence properties is the ability to form biofilms (dental plaque) on tooth surfaces. The development of anti-quorum-sensing drugs that attenuate virulence might represent an attractive alternative to conventional antibiotic therapy, considering the fact that these antibacterial compounds are less likely to induce the development of resistant bacteria. Such a “proof of concept” has already been provided by mimics of the acylated homoserine lactone signalling molecules, such as synthetic derivatives of natural furanones, which are able to inhibit in vivo biofilm development of Pseudomonas aeruginosa [13], and when covalently bound to surfaces those of Staphylococcus epidermidis [14]. None of the quorum sensing blockers tested in animal models so far was suitable for human use

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