| dc.description.abstract | Staphylococcus epidermidis has developed from a skin and mucus commensal to an opportunistic pathogen, and is frequently causing infections in medical implants. Its ability to form biofilm on implant surfaces makes these infections extremely persistent, and re-operation is in most cases the only option to clear these infections. Quorum-sensing, chemical cell-to-cell communication between bacteria has shown to regulate several virulence factors in important pathogens, such as biofilm formation and toxin production. Molecules with the ability to quench this quorum sensing could therefore lead to new therapies, targeting traits crucial for bacterial pathogenesis. Thiophenones are quorum sensing inhibitors, showing ability to inhibit AI-2 mediated communication. When using thiophenones a decrease in biofilm formation in Vibrio harveyi, Escherichia coli and S.epidermidis has been observed. The aim of this study was to investigate the effect of different thiophenones on virulence factors in S.epidermidis. The effect of thiophenones on S.epidermidis biofilm formation in combination with antibiotics was tested, as well as persister cell formation and adherence to eukaryotic cells. An in vivo model for studying Staphylococcal infections was also established using C.elegans. This model was used to look at the effect of a thiophenone on recovery of C.elegans after infection. All thiophenones tested showed inhibition of AI-2 communication in V.harveyi in a bioluminescence assay. Thiophenones in combination with antibiotics did not show to have any additive effect on S.epidermidis biofilm formation. To isolate and test the effect of thiophenones on persister cells proved difficult, and no conclusion regarding the effect of thiophenones could be drawn. S.epidermidis showed low binding to Caco-2 cells, and it was therefore difficult to determine if thiophenones had any effect on the ability to bind to eukaryotic cells. Two S.epidermidis strains and one S.aureus strain was tested for their ability to cause infection in C.elegans. Only worms grown on S.aureus showed decreased survival after 7 days of infection. The effect of a thiophenone on C.elegans recovery from 24 h infection by S.aureus was tested, but no persistent infection was detected. It was therefore difficult to make any conclusion about the effect of thiophenone on recovery, but the thiophenone concentration was shown not to be toxic for the worms. Optimization of the different methods is needed to make any conclusions on thiophenones effect on the different virulence factors in S.epidermidis. | eng |