摘要
抽象图像
环境化学污染引起的抗生素抗性基因的富集和传播进一步加剧了对人类健康和生态安全的威胁。已知几种化合物通过诱导活性氧（ROS）、增加细胞膜通透性、增强调节基因表达等途径诱导R质粒介导的缀合。到目前为止，在模型和相关机制的研究方面还没有取得实质性突破。在这里，我们使用信息素响应质粒pCF10建立了一个新的缀合模型，并证实了与环境相关浓度的五种双酚（BP）可以显著促进质粒pCF10介导的ARGs在粪大肠杆菌中的缀合，与未处理的细胞相比，缀合高达4.5倍。使用qPCR、基因敲除和UHPLC，我们使用双酚A（BPA）作为BPs的模型来探索这一现象背后的机制，并证明BPA可以上调信息素的表达，促进细菌聚集，甚至可以直接激活作为信息素的结合，而不是产生ROS和增强细胞膜通透性。有趣的是，数学分析结果表明，大多数BP的信息素效应比合成信息素cCF10更有效。这些发现为BP的环境行为和生物效应提供了新的见解，并为研究环境化学污染引起的ARGs的富集和扩散提供了新方法和理论。
Abstract
Abstract Image
The enrichment and spread of antibiotic resistance genes (ARGs) induced by environmental chemical pollution further exacerbated the threat to human health and ecological safety. Several compounds are known to induce R plasmid-mediated conjugation through inducing reactive oxygen species (ROS), increasing cell membrane permeability, enhancing regulatory genes expression, and so forth. Up to now, there has been no substantial breakthrough in the studies of models and related mechanisms. Here, we established a new conjugation model using pheromone-responsive plasmid pCF10 and confirmed that five kinds of bisphenols (BPs) at environmentally relevant concentrations could significantly promote the conjugation of ARGs mediated by plasmid pCF10 in E. faecalis by up to 4.5-fold compared with untreated cells. Using qPCR, gene knockout and UHPLC, we explored the mechanisms behind this phenomenon using bisphenol A (BPA) as a model of BPs and demonstrated that BPA could upregulate the expression of pheromone, promote bacterial aggregation, and even directly activate conjugation as a pheromone instead of producing ROS and enhancing cell membrane permeability. Interestingly, the result of mathematical analysis showed that the pheromone effect of most BPs is more potent than that of synthetic pheromone cCF10. These findings provide new insight into the environmental behavior and biological effect of BPs and provided new method and theory to study on enrichment and spread of ARGs induced by environmental chemical pollution.

https://pubs.acs.org/doi/abs/10.1021/acs.est.2c05349