Abstract

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.

Highlights

  • IntroductionWith the advent of HIV and other immunocompromising diseases and modern-day surgeries, an increase in Candida infections has been reported

  • Exposure of the Ag-Cu-Co trimetallic nanoparticle-induced apoptosis in C. auris cells and we further studied the effect of the nanoparticle over cell cycle in C. auris membrane depolarization and an association with apoptosis and DNA fragmentation in

  • The phytochemicals in Salvia officinalis extract plays a significant role in controlling the size, morphology and size distribution of the as-prepared nanoparticles

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Summary

Introduction

With the advent of HIV and other immunocompromising diseases and modern-day surgeries, an increase in Candida infections has been reported. These infections have been recognized as a global threat, further amplified by the spread of multidrug-resistant. An emerging threat to immunocompetent and immunocompromised patients worldwide, is often resistant to available antifungal drugs [1,2,3]. This species is generally unresponsive to fluconazole and often resistant to amphotericin B and echinocandins are the first-line drugs for treating C. auris infections [4]

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