Phytogenic Fabrication of Ag-Fe Bimetallic Nanoparticles for Cell Cycle Arrest and Apoptosis Signaling Pathways in Candida auris by Generating Oxidative Stress.

Majid Rasool Kamli,Maqsood Ahmad Malik,Jamal S M Sabir,Nahid H Hajrah,Vartika Srivastava,Aijaz Ahmad,Arif Ali

doi:10.3390/antiox10020182

Abstract

Novel green synthetic nanomedicines have been recognized as alternative therapies with the potential to be antifungal agents. Apoptosis induction, cell cycle arrest and activation of the antioxidant defense system in fungal cells have also gained attention as emerging drug targets. In this study, a facile and biodegradable synthetic route was developed to prepare Ag–Fe bimetallic nanoparticles using aqueous extract of Beta vulgaris L. Surface plasmon resonance of Beta vulgaris-assisted AgNPs nanoparticles was not observed in the UV-visible region of Ag–Fe bimetallic NPs, which confirms the formation of Ag–Fe nanoparticles. Beta vulgaris-assisted Ag–Fe NPs were characterized by FTIR spectroscopy, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction and TGA-DTG analysis for their structural and morphological properties. The as-prepared Ag–Fe NPs were well dispersed and spherical with the average particle size of 15 nm. The antifungal activity of these Ag–Fe NPs against clinical isolates of Candida auris was determined by broth microdilution and cell viability assays. For insights into mechanisms, induction of apoptosis and triggering cell cycle arrest were studied following standard protocols. Furthermore, analysis of antioxidant defense enzymes was determined spectrophotometrically. Antifungal susceptibility results revealed high antifungal activity with MIC values ranging from 0.19 to 0.39 µg/mL. Further studies showed that Ag–Fe NPs were able to induce apoptosis, cell cycle arrest in G2/M phase and disturbances in primary and secondary antioxidant enzymes. This study presents the potential of Ag–Fe NPs to inhibit and potentially eradicate C. auris by inducing apoptosis, cell cycle arrest and increased levels of oxidative stress.

Highlights

The possible biosynthesis of Ag–Fe nanoparticles was physically observed in the color change from light yellow to dark brown upon the addition of Beta vulgaris L. extract to the mixture
Upon the addition of the aqueous extract of Beta vulgaris into the Fe3+ and Ag+ ions aqueous solution, the surface plasmon resonance (SPR) peak at 450 nm drastically disappeared and a peak (343 nm) corresponding to Fe nanoparticles (Fe NPs) showed an increase in peak intensity with a plasmon shifted to 310 nm and broadening of absorption band for
The present study demonstrated that Ag–Fe NPs affect C. auris growth and survival negatively

Summary

Introduction

Candida auris, spreading across the globe and responsible for hospital outbreaks, is considered a global health threat with a high mortality rate of approximately 30–60% [1]. Due to this pathogen’s metabolic plasticity, allowing it to thrive in different habitats, frequent hospital outbreaks have been reported worldwide. C. auris isolates have been reported to be resilient to at least one antifungal class [2]. These challenges further complicate the treatment procedures, in immunocompromised patient

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Conclusion