Zinc oxide and silver nanoparticles toxicity in the baker's yeast, <i>Saccharomyces cerevisiae</i>

Engineered nanomaterials (ENMs) are increasingly incorporated into a variety of commercial applications and consumer products; however, ENMs may possess cytotoxic properties due to their small size. This study assessed the effects of two commonly used ENMs, zinc oxide nanoparticles (ZnONPs) and silver nanoparticles (AgNPs), in the model eukaryote Saccharomyces cerevisiae. A collection of ≈4600 S. cerevisiae deletion mutant strains was used to deduce the genes, whose absence makes S. cerevisiae more prone to the cytotoxic effects of ZnONPs or AgNPs. We demonstrate that S. cerevisiae strains that lack genes involved in transmembrane and membrane transport, cellular ion homeostasis, and cell wall organization or biogenesis exhibited the highest sensitivity to ZnONPs. In contrast, strains that lack genes involved in transcription and RNA processing, cellular respiration, and endocytosis and vesicular transport exhibited the highest sensitivity to AgNPs. Secondary assays confirmed that ZnONPs affected cell wall function and integrity, whereas AgNPs exposure decreased transcription, reduced endocytosis, and led to a dysfunctional electron transport system. This study supports the use of S. cerevisiae Gene Deletion Array as an effective high-throughput technique to determine cellular targets of ENM toxicity.工程化纳米材料（Engineered nanomaterials, ENMs）正日益被应用于各类商业场景与消费品中；然而，ENMs凭借其极小的尺寸，可能具备细胞毒性。本研究以模式真核生物酿酒酵母（Saccharomyces cerevisiae）为模型，评估了两种常用ENMs——氧化锌纳米颗粒（zinc oxide nanoparticles, ZnONPs）与银纳米颗粒（silver nanoparticles, AgNPs）的细胞毒性效应。本研究采用了包含约4600株酿酒酵母缺失突变菌株的集合，以鉴定出那些缺失后会使酿酒酵母更易受到ZnONPs或AgNPs细胞毒性影响的基因。研究结果显示，缺失参与跨膜运输与膜转运、细胞离子稳态以及细胞壁组织或生物合成相关基因的酿酒酵母菌株，对ZnONPs呈现出最高的敏感性。与之相反，缺失参与转录与RNA加工、细胞呼吸以及内吞作用与囊泡转运相关基因的菌株，对AgNPs呈现出最高的敏感性。后续验证实验证实，ZnONPs会影响细胞壁的功能与完整性；而AgNPs暴露则会降低转录水平、削弱内吞作用，并导致电子传递系统功能异常。本研究证实，酿酒酵母基因缺失阵列（S. cerevisiae Gene Deletion Array）是一种可用于确定ENMs毒性细胞靶点的高效高通量技术。