Therapeutic potential of a novel anti quorum-sensing agent, incorporated into a sustained released device, against oral fungal biofilms

Objectives: Oral candidiasis is a superficial infection caused mainly by Candida albicans. This yeast like fungus can rapidly form on surfaces of oral cavity, biofilms which are inherently resistant to antifungal treatments. Quorum sensing (QS) is closely associated with biofilm formation and are associated with increasing fungal pathogenicity. We investigated the ability of the novel QS quencher thiazolidinedione-8 (S-8) to affect C. albicans pathogenicity. We investigated the possibility of incorporating S-8 in a sustained-release-membrane (SRM) to maximize its pharmaceutical potential against fungal biofilm.

Methods: S-8 was synthesized in our laboratory and incorporated into a sustained released membrane (SRM). Effect of S-8 on C. albicans biofilm formation and detachment was investigated by XTT and SEM methods. Adherence of candida exposed to S-8 to mammalian cells was tested by using fluorescence microscopy. Biofilm thickness and exopolysaccharide production of fungal cells treated with SRM containing S-8 were analyzed with CLSM. Biofilm-associated genes expression of C. albicans due to S-8 treatment was evaluated using Real Time RT PCR.

Results: We found prolonged, time-dependent anti-fungal biofilm effect of S-8 released from the formulated SRM. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at 4- to 8-fold concentrations lower than the minimum inhibitory concentration (MIC). This agent also significantly inhibits yeast-hyphal transition and fungal attachment to mammalian cells. It reduces hydrophobicity and affects biofilm structure. The expression levels of genes associated with biofilm formation, adhesion and filamentation were altered by S-8.

Conclusions: We have intergraded in this research two fields: SRM and anti quorum sensing agent. This is a new and exciting concept in medicine and dentistry. The successful formulation of a SRM incorporating quorum sensing quencher with an anti-biofilm effect is novel and bears promising clinical effects.