摘要
       抗生素耐药性是威胁公众健康的全球性问题。细菌物种之间的水平基因转移（HGT）对抗生素耐药性的传播有很大贡献。偶联是导致抗生素抗性基因（ARGs）传播的主要HGT途径之一。抗抑郁药物通常是治疗严重抑郁症的抗精神病药物，并且经常在水生环境中检测到。然而，人们对抗抑郁药如何对细菌产生压力以及这种作用是否能促进结合知之甚少。在此，我们报道了常用的抗抑郁药，舍曲林、度洛西汀、氟西汀和安非他酮，可以促进环境和临床相关质粒携带的质粒携带的多药耐药基因的偶联转移。值得注意的是，临床相关浓度的抗抑郁药显著增强了质粒在细菌属之间的转移。我们还通过流式细胞术分析、全基因组RNA测序和蛋白质组学分析揭示了增强偶联转移的潜在机制。抗抑郁药诱导活性氧的产生和SOS反应，增加细胞膜通透性，并上调结合相关基因的表达。鉴于HGT在ARGs传播中的作用，我们的研究结果强调了谨慎开具抗抑郁药处方的重要性，以及抗抑郁药与抗生素耐药性增加之间的潜在联系。
Abstract
Antibiotic resistance is a global concern threatening public health. Horizontal gene transfer (HGT) between bacterial species contributes greatly to the dissemination of antibiotic resistance. Conjugation is one of the major HGT pathways responsible for the spread of antibiotic resistance genes (ARGs). Antidepressant drugs are commonly prescribed antipsychotics for major depressive disorders and are frequently detected in aquatic environments. However, little is known about how antidepressants stress bacteria and whether such effect can promote conjugation. Here, we report that commonly prescribed antidepressants, sertraline, duloxetine, fluoxetine, and bupropion, can promote the conjugative transfer of plasmid-borne multidrug resistance genes carried by environmentally and clinically relevant plasmids. Noteworthy, the transfer of plasmids across bacterial genera is significantly enhanced by antidepressants at clinically relevant concentrations. We also reveal the underlying mechanisms of enhanced conjugative transfer by employing flow cytometric analysis, genome-wide RNA sequencing and proteomic analysis. Antidepressants induce the production of reactive oxygen species and the SOS response, increase cell membrane permeability, and upregulate the expression of conjugation relevant genes. Given the contribution of HGT in the dissemination of ARGs, our findings highlight the importance of prudent prescription of antidepressants and to the potential connection between antidepressants and increasing antibiotic resistance.

https://ami-journals.onlinelibrary.wiley.com/doi/full/10.1111/1462-2920.16165