Bio-Inspired Silver Nanoparticles Impose Metabolic and Epigenetic Toxicity to Saccharomyces cerevisiae

Silver nanoparticles (AgNPs) have many applications in various fields, including biomedical applications. Due to the broad range of applications, they are considered as the leading fraction of manufactured nanoparticles. AgNPs are synthesized by different types of chemical and biological (green) methods. Previously, biologically synthesized AgNPs were considered safe for the environment and humans. However, new toxicity evidence have initiated a more careful assessment to delineate the toxicity mechanisms associated with these nanoparticles. This study demonstrates the use of aqueous gooseberry extract for AgNP preparation in a time- and cost-effective way. Ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, and dynamic light scattering confirm the formation of AgNPs, with an average size between 50 and 100 nm. Untargeted ¹H-nuclear magnetic resonance-based metabolomics revealed manyfold up- and down-regulation in the concentration of 55 different classes of annotated metabolites in AgNP-exposed yeast Saccharomyces cerevisiae cells. Based on their chemical nature and cellular functions, these metabolites are classified into amino acids, glycolysis and the tricarboxylic acid (TCA) cycle, organic acids, nucleotide metabolism, urea cycle, and lipid metabolism. Transcriptome analysis revealed that the genes involved in oxidative stress mitigation maintain their expression levels, whereas the genes of the TCA cycle and lipid metabolism show drastic down-regulation upon AgNP exposure. Moreover, they can induce alteration in histone epigenetic marks by altering the methylation and acetylation of selected histone H3 and H4 proteins. Altogether, we conclude that the selected dose of biologically synthesized AgNPs impose toxicity by modulating the transcriptome, epigenome, and metabolome of eukaryotic cells, which eventually cause disequilibrium in cellular metabolism leading to toxicity.