Synergistic Effect Between Taurine-Induced Silver Ion and Itraconazole Against Azole-Resistant Candida Species and Candida auris

Abstract

AIM: To combat the rising threat of azole-resistant Candida species and the global concern of Candida auris, exploring combination therapies with existing antimicrobial agents is critical. BACKGROUND: Azoles 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: We evaluated the antifungal activity of taurine-induced silver ions (Tau-Ag), prepared by induction from silver-incorporated mesoporous bioactive glass, and its synergistic effects with itraconazole. RESULTS: 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, cytotoxicity and in vivo toxicity were observed at the MICs. In the investigation of antifungal mechanisms, the reactive oxygen species (ROS) level significantly increased when Candida spp. treated with Tau-Ag. Biofilm formation inhibition assays found 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, Tau-Ag showed synergistic antifungal effects in combination with itraconazole, effectively restoring its activity. In C. elegans models, the Tau-Ag-treated groups, and the combination treatment group with itraconazole revealed effectiveness against MDR C. albicans ATCC 10231. CONCLUSIONS: 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.

Keywords

• Azole-resistant
• Candida spp.
• Tau-Ag
• Itraconazole
• Synergistic effect
• Caenorhabditis elegans model