Synergistic effect between taurine-induced silver ion and itraconazole against azole-resistant Candida species and Candida auris

Abstract

Background: Azole antifungals are the first-line choice for treating candidiasis within a limited antifungal option. However, azole-resistant Candida species have increased rapidly, causing severe clinical threats, especially multidrug-resistant (MDR) isolates. The emergence of Candida auris has also caused global concerns recently. Methods: Herein, we evaluated the antifungal activity of taurine-induced silver ions (Tau-Ag), prepared by the induction from silver-incorporated mesoporous bioactive glass to address this issue. Results: Our data demonstrated that minimum inhibitory concentrations (MICs) of Tau-Ag ranged from 0.020 to 0.078 mg/mL in 24h and from 0.039 to 0.156 mg/mL in 48h. No hemolysis and cytotoxicity were observed at the MICs. Furthermore, no in vivo toxicity related to Tau-Ag was observed in a Caenorhabditis elegans model. In the investigation of antifungal mechanisms, we observed that the reactive oxygen species (ROS) level significantly increased when Candida spp. treated with Tau-Ag. Biofilm formation inhibition assays found that Tau-Ag may penetrate the biofilm and eliminate biofilm-forming cells. In the time-kill method, Tau-Ag showed a long-lasting fungistatic effect and superior antifungal effect compared to itraconazole alone. Furthermore, TauAg showed synergistic antifungal effects in combination with itraconazole, effectively restoring its activity. Conclusion: Our results confirmed the potential of Tau-Ag and its combination use with itraconazole to serve as a novel antifungal agent to combat the plight of administration on azole-resistant and MDR Candida spp. and C. auris.