JAC Advance Access originally published online on December 20, 2008
Journal of Antimicrobial Chemotherapy 2009 63(2):309-316; doi:10.1093/jac/dkn501
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Original research |
Furanones, potential agents for preventing Staphylococcus epidermidis biofilm infections?
1 Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway 2 Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
Received 16 September 2008; returned 5 November 2008; revised 13 November 2008; accepted 18 November 2008
* Corresponding author. Tel: +47-22-84-03-63; Fax: +47-22-84-03-02; E-mail: jessiclo{at}odont.uio.no
Objectives: Staphylococcus epidermidis is often associated with biofilm infections related to medical implants. The aim of the present study was to find furanones that decrease biofilm formation without irritative or genotoxic effects, or effects on S. epidermidis growth.
Methods: After screening including bioluminescence and biofilm assays, 2 furanones out of 11 were chosen for further studies. MIC values of the two furanones were established to determine whether biofilm inhibition effects were ascribed to inhibition of bacterial growth. To further investigate interference with communication, the effect of the furanones was tested in the presence of the autoinducer-2 precursor (S)-4,5-dihydroxy-2,3-pentanedione. The furanones were tested for possible irritative effects by the Hens egg test chorioallantoic membrane procedure. Finally, potential genotoxic effects in mice were assessed by a membrane array, and effects on global gene expression were investigated by using a microarray representing 30 000 genes of the mouse genome.
Results: From the bioluminescence assay, 4 furanones out of 11 were chosen for further biofilm analyses. Biofilm formation by S. epidermidis was significantly decreased by the four furanones tested at concentrations not affecting microbial growth. Two furanones were chosen for further studies: one that decreased biofilm statistically more than the others and one containing two bromo substituents. The two furanones were found to be non-irritative and non-genotoxic at the concentrations used.
Conclusions: Furanones may inhibit biofilm formation through interference with quorum sensing and thus represent promising agents for protecting surfaces from being colonized by S. epidermidis.
Keywords: antibiotic resistance , genotoxicity , implants , irritability