Antibiotic resistance is a serious global threat for public health. Considering the high abundance of cell-free DNA encoding antibiotic resistance genes (ARGs) in both clinical and environmental settings, natural transformation is an important horizontal gene transfer pathway to transmit antibiotic resistance. It is acknowledged that antibiotics are key drivers for disseminating antibiotic resistance, yet the contributions of non-antibiotic pharmaceuticals on transformation of ARGs are overlooked. In this study, we report that some commonly consumed non-antibiotic pharmaceuticals, at clinically and environmentally relevant concentrations, significantly facilitated the spread of antibiotic resistance through the uptake of exogenous ARGs. This included nonsteroidal anti-inflammatories, ibuprofen, naproxen, diclofenac, the lipid-lowering drug, gemfibrozil, and the β-blocker propranolol. Based on the results of flow cytometry, whole-genome RNA sequencing and proteomic analysis, the enhanced transformation of ARGs was affiliated with promoted bacterial competence, enhanced stress levels, over-produced reactive oxygen species and increased cell membrane permeability. In addition, a mathematical model was proposed and calibrated to predict the dynamics of transformation during exposure to non-antibiotic pharmaceuticals. Given the high consumption of non-antibiotic pharmaceuticals, these findings reveal new concerns regarding antibiotic resistance dissemination exacerbated by non-antibiotic pharmaceuticals.

中文翻译：

---

非抗生素药物通过细菌转化增强外源抗生素抗性基因的传递。

抗生素耐药性是对公共卫生的严重全球威胁。考虑到在临床和环境环境中编码抗生素抗性基因 (ARG) 的大量无细胞 DNA，自然转化是传递抗生素抗性的重要水平基因转移途径。众所周知，抗生素是传播抗生素耐药性的关键驱动因素，但人们忽视了非抗生素药物对 ARGs 转化的贡献。在这项研究中，我们报告了一些常用的非抗生素药物，在临床和环境相关浓度下，通过吸收外源性 ARGs 显着促进了抗生素耐药性的传播。这包括非甾体抗炎药、布洛芬、萘普生、双氯芬酸、降脂药、吉非罗齐和β受体阻滞剂普萘洛尔。基于流式细胞术、全基因组 RNA 测序和蛋白质组学分析的结果，ARGs 的增强转化与增强的细菌能力、增强的应激水平、过量产生的活性氧和增加的细胞膜通透性有关。此外，提出并校准了一个数学模型，以预测在暴露于非抗生素药物期间的转化动态。鉴于非抗生素药物的大量消费，这些发现揭示了对非抗生素药物加剧的抗生素耐药性传播的新担忧。ARGs 的增强转化与增强的细菌能力、增强的压力水平、过量产生的活性氧和增加的细胞膜通透性有关。此外，提出并校准了一个数学模型，以预测在暴露于非抗生素药物期间的转化动态。鉴于非抗生素药物的大量消费，这些发现揭示了对非抗生素药物加剧的抗生素耐药性传播的新担忧。ARGs 的增强转化与增强的细菌能力、增强的压力水平、过量产生的活性氧和增加的细胞膜通透性有关。此外，提出并校准了一个数学模型，以预测在暴露于非抗生素药物期间的转化动态。鉴于非抗生素药物的大量消费，这些发现揭示了对非抗生素药物加剧的抗生素耐药性传播的新担忧。