摘要
      结合质粒介导的水平基因转移（HGT）对细菌进化和抗生素抗性基因（ARGs）的传播有很大贡献。除了广泛使用抗生素带来的选择性压力外，环境化学污染物还促进了抗生素耐药性的传播，从而对生态环境构成严重威胁。目前，大多数研究都集中在环境化合物对R质粒介导的缀合转移的影响上，而信息素诱导的缀合在很大程度上被忽视了。在本研究中，我们探讨了雌二醇在促进粪肠球菌pCF10质粒偶联转移中的信息素作用和潜在的分子机制。与环境相关的雌二醇浓度显著增加了pCF10的偶联转移，最大频率为3.2×10-2，与对照相比变化高达3.5倍。暴露于雌二醇通过增加ccfA的表达来诱导信息素信号级联的激活。此外，雌二醇可能直接与信息素受体PrgZ结合，促进pCF10的诱导，最终增强pCF10结合转移。这些发现为雌二醇及其同源物在增加抗生素耐药性和潜在生态风险中的作用提供了有价值的见解。
Abstract
Horizontal gene transfer (HGT) mediated by conjugative plasmids greatly contributes to bacteria evolution and the transmission of antibiotic resistance genes (ARGs). In addition to the selective pressure imposed by extensive antibiotic use, environmental chemical pollutants facilitate the dissemination of antibiotic resistance, consequently posing a serious threat to the ecological environment. Presently, the majority of studies focus on the effects of environmental compounds on R plasmid-mediated conjugation transfer, and pheromone-inducible conjugation has largely been neglected. In this study, we explored the pheromone effect and potential molecular mechanisms of estradiol in promoting the conjugative transfer of pCF10 plasmid in Enterococcus faecalis. Environmentally relevant concentrations of estradiol significantly increased the conjugative transfer of pCF10 with a maximum frequency of 3.2 × 10-2, up to 3.5-fold change compared to that of control. Exposure to estradiol induced the activation of pheromone signaling cascade by increasing the expression of ccfA. Furthermore, estradiol might directly bind to the pheromone receptor PrgZ and promote pCF10 induction and finally enhance the conjugative transfer of pCF10. These findings cast valuable insights on the roles of estradiol and its homolog in increasing antibiotic resistance and the potential ecological risk.

https://www.sciencedirect.com/science/article/abs/pii/S0304389423003692