Work

In vitro synergistic antifungal activity of silybin-posaconazole combination against Candida auris

Year: 2026

Type: article

Abstract: Background Candida auris infections pose a severe global public health threat. The hepatotoxicity of conventional azole antifungals and biofilm-mediated drug resistance adversely affect their clinical application. The natural component silybin (SLB) has both hepatoprotective and antimicrobial activities. Methods This study was conducted in accordance with the CLSI M27-A4 standard, employing the broth microdilution plate method to evaluate the efficacy of SLB combined with itraconazole (ITR), voriconazole (VOR), posaconazole (POS) and fluconazole (FLC) against 10 C. auris strains. Synergistic effects were determined by measuring minimum inhibitory concentrations (MICs) and fractional inhibition concentration indices (FICIs). Potential synergistic mechanisms were investigated using ergosterol quantification, biofilm inhibition assay, reactive oxygen species (ROS) detection, Real-Time Quantitative PCR, SYTO9/PI double staining assay, and XTT assay. Results Antifungal susceptibility testing showed that synergistic effects were most frequently observed when SLB was combined with POS (70% of strains), followed by SLB-VOR (50%) and SLB-ITR (30%). No synergism was detected for the SLB-FLC combination, while antagonism was observed in one strain for the SLB-ITR combination. The SLB-POS combination reduced ergosterol content, inhibited biofilm formation, and decreased the viability of preformed mature biofilms. It induced ROS accumulation, downregulated the expression of biofilm-associated genes ( bcr1 , efg1 , scf1 , mkc1 , erg2 , erg11 , als5 ) under planktonic conditions, and suppressed biofilm proliferative activity. Conclusion The SLB-POS combination exhibits synergistic antifungal activity against C. auris. Its activity is associated with multiple pathways, including elevated oxidative stress responses and reduced ergosterol content. In addition, this combination downregulates biofilm-related gene expression and impairs the capacity of planktonic cells to form biofilms. These findings provide preliminary experimental evidence for addressing C. auris drug resistance and support further investigation of this combination as a therapeutic strategy with an improved safety-efficacy profile and potential for clinical translation. Notably, the in vitro synergistic concentration exceeds the maximum oral bioavailable levels in vivo , and translational potential requires further in vivo verification.

Source: Frontiers in Microbiology

DOI: 10.3389/fmicb.2026.1881511