Candida auris is an emergent multidrug-resistant pathogen that can lead to severe bloodstream infections associated with high mortality rates, especially in hospitalized individuals suffering from serious medical problems. As Candida auris is often multidrug-resistant, there is a persistent demand for new antimycotic drugs with novel antifungal action mechanisms. Here, we reported the facile, one-pot, one-step biosynthesis of biologically active Ag-Cu-Co trimetallic nanoparticles using the aqueous extract of Salvia officinalis rich in polyphenols and flavonoids. These medicinally important phytochemicals act as a reducing agent and stabilize/capping in the nanoparticles' fabrication process. Fourier Transform-Infrared, Scanning electron microscopy, Transmission Electron Microscopy, Energy dispersive X-Ray, X-ray powder diffraction and Thermogravimetric analysis (TGA) measurements were used to classify the as-synthesized nanoparticles. Moreover, we evaluated the antifungal mechanism of as-synthesized nanoparticles against different clinical isolates of C. auris. The minimum inhibitory concentrations and minimum fungicidal concentrations ranged from 0.39-0.78 μg/mL and 0.78-1.56 μg/mL. Cell count and viability assay further validated the fungicidal potential of Ag-Cu-Co trimetallic nanoparticles. The comprehensive analysis showed that these trimetallic nanoparticles could induce apoptosis and G2/M phase cell cycle arrest in C. auris. Furthermore, Ag-Cu-Co trimetallic nanoparticles exhibit enhanced antimicrobial properties compared to their monometallic counterparts attributed to the synergistic effect of Ag, Cu and Co present in the as-synthesized nanoparticles. Therefore, the present study suggests that the Ag-Cu-Co trimetallic nanoparticles hold the capacity to be a lead for antifungal drug development against C. auris infections.
Keywords: Candida auris; G2/M arrest; apoptosis; cell cycle; green synthesis; nanoparticles.