Combination Effect of Novel Bimetallic Ag-Ni Nanoparticles with Fluconazole against Candida albicans.

ABSTRACT

The increasing frequency of antifungal drug resistance among pathogenic yeast "Candida" has posed an immense global threat to the public healthcare sector. The most notable species of Candida causing most fungal infections is Candida albicans. Furthermore, recent research has revealed that transition and noble metal combinations can have synergistic antimicrobial effects. Therefore, a one-pot seedless biogenic synthesis of Ag-Ni bimetallic nanoparticles (Ag-Ni NPs) using Salvia officinalis aqueous leaf extract is described. Various techniques, such as UV-vis, FTIR, XRD, SEM, EDX, and TGA, were used to validate the production of Ag-Ni NPs. The antifungal susceptibility of Ag-Ni NPs alone and in combination with fluconazole (FLZ) was tested against FLZ-resistant C. albicans isolate. Furthermore, the impacts of these NPs on membrane integrity, drug efflux pumps, and biofilms formation were evaluated. The MIC (1.56 µg/mL) and MFC (3.12 µg/mL) results indicated potent antifungal activity of Ag-Ni NPs against FLZ-resistant C. albicans. Upon combination, synergistic interaction was observed between Ag-Ni NPs and FLZ against C. albicans 5112 with a fractional inhibitory concentration index (FICI) value of 0.31. In-depth studies revealed that Ag-Ni NPs at higher concentrations (3.12 µg/mL) have anti-biofilm properties and disrupt membrane integrity, as demonstrated by scanning electron microscopy results. In comparison, morphological transition was halted at lower concentrations (0.78 µg/mL). From the results of efflux pump assay using rhodamine 6G (R6G), it was evident that Ag-Ni NPs blocks the efflux pumps in the FLZ-resistant C. albicans 5112. Targeting biofilms and efflux pumps using novel drugs will be an alternate approach for combatting the threat of multi-drug resistant (MDR) stains of C. albicans. Therefore, this study supports the usage of Ag-Ni NPs to avert infections caused by drug resistant strains of C. albicans.