摘要

       细菌的抗生素耐药性对全球人类健康构成日益严重的威胁。抗生素抗性基因 (ARG) 的水平基因转移 (HGT) 被认为是抗生素抗性传播的主要因素。银纳米粒子 (AgNPs) 广泛用于个人护理产品中作为抗菌剂。虽然已知重金属会引起细菌的抗生素耐药性，但环境中的 AgNPs 是否可以刺激 ARGs 的 HGT 尚不清楚。在这里，我们报告说，AgNPs 和离子银 Ag+，在环境相关和亚致死浓度下，促进质粒携带的 ARGs 跨细菌属的结合转移（从供体大肠杆菌 K-12 LE392 到受体恶臭假单胞菌 KT2440） .通过检测氧化应激和细胞膜通透性，结合全基因组 RNA 测序和蛋白质组学分析，揭示了 Ag+- 或 AgNPs 促进的 HGT 的潜在机制。结果发现，Ag+ 和 AgNPs 暴露都会诱导各种细菌反应，包括活性氧 (ROS) 生成、膜损伤和 SOS 反应。这项研究揭示了环境水平的 AgNPs 和 Ag+ 促进 ARGs 传播的潜在生态风险，并强调了对纳米颗粒和重金属管理的担忧。

       Antibiotic resistance in bacteria is a growing threat to global human health. Horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) is recognized as the primary contributor to antibiotic resistance dissemination. Silver nanoparticles (AgNPs) are widely used in personal care products as antimicrobial agents. While heavy metals are known to induce antibiotic resistance in bacteria, it is not known whether AgNPs in the environment can stimulate the HGT of ARGs. Here, we report that both AgNPs and ionic silver Ag+, at environmentally relevant and sub-lethal concentrations, facilitate the conjugative transfer of plasmid-borne ARGs across bacterial genera (from the donor Escherichia coli K-12 LE392 to the recipient Pseudomonas putida KT2440). The underlying mechanisms of the Ag+- or AgNPs-promoted HGT were unveiled by detecting oxidative stress and cell membrane permeability, combined with genome-wide RNA sequencing and proteomic analyses. It was found that both Ag+ and AgNPs exposure induced various bacterial responses that included reactive oxygen species (ROS) generation, membrane damage and the SOS response. This study exposes the potential ecological risks of environmental levels of AgNPs and Ag+ for promoting the spread of ARGs and highlights concerns regarding the management of nanoparticles and heavy metals.

https://www.sciencedirect.com/science/article/abs/pii/S0043135419310036