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.

中文翻译：

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抗抑郁药通过水平接合基因转移促进抗生素耐药性的传播

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) 极大地促进了抗生素耐药性的传播。结合是负责抗生素抗性基因 (ARG) 传播的主要 HGT 途径之一。抗抑郁药是治疗重度抑郁症的常用抗精神病药物，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。在这里，我们报告常用处方抗抑郁药舍曲林、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接合转移。值得注意的是，临床相关浓度的抗抑郁药显着增强了质粒跨细菌属的转移。我们还通过采用流式细胞术分析、全基因组 RNA 测序和蛋白质组学分析揭示了增强结合转移的潜在机制。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 传播中的贡献，我们的研究结果强调了谨慎处方抗抑郁药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。我们还通过采用流式细胞术分析、全基因组 RNA 测序和蛋白质组学分析揭示了增强结合转移的潜在机制。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 传播中的贡献，我们的研究结果强调了谨慎处方抗抑郁药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。我们还通过采用流式细胞术分析、全基因组 RNA 测序和蛋白质组学分析揭示了增强结合转移的潜在机制。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 传播中的贡献，我们的研究结果强调了谨慎处方抗抑郁药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。并上调结合相关基因的表达。鉴于 HGT 在 ARGs 传播中的贡献，我们的研究结果强调了谨慎处方抗抑郁药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。并上调结合相关基因的表达。鉴于 HGT 在 ARGs 传播中的贡献，我们的研究结果强调了谨慎处方抗抑郁药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。