Li Haibei, Li Xinmei, Chen Tianjiao, Yang Zhongwei, Shi Danyang, Yin Jing, Yang Dong, Zhou Shuqing, Li Junwen, Jin Min
Department of Environment and Health, Tianjin Institute of Environmental & Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin 300050, China.
Department of Environment and Health, Tianjin Institute of Environmental & Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin 300050, China.
J Hazard Mater. 2023 Jun 15;452:131371. doi: 10.1016/j.jhazmat.2023.131371. Epub 2023 Apr 5.
The emergence of disinfectant-resistant pathogens in water is a major threat to public health. However, whether human-consumed pharmaceuticals can induce bacterial resistance to disinfectants remains unclear. Herein, Escherichia coli was exposed to 12 antidepressants, and susceptibility of antidepressant-induced chloramphenicol (CHL)-resistant mutants to disinfectants was tested. Whole genome sequencing, global transcriptomic sequencing, and real-time quantitative polymerase chain reaction were used to elucidate the underlying mechanisms. We observed that duloxetine, fluoxetine, amitriptyline, and sertraline significantly increased the mutation frequency of E. coli against CHL by 15- to 2948-fold. The resultant mutants increased the average MIC of sodium hypochlorite, benzalkonium bromide, and triclosan roughly 2- to 8-fold. Consistently, marRAB and acrAB-tolC genes, together with ABC transporter genes (e.g., yddA, yadG, yojI, and mdlA), were triggered to increase the efflux of disinfectants out of the cell, while ompF was inhibited, reducing disinfectant penetration into the cell. Additionally, the occurrence of DNA mutations in marR and acrR in the mutants was observed, potentially resulting in increased synthesis of the AcrAB-TolC pump. This study indicates that pharmaceutical exposure may create disinfectant-resistant bacteria, which may then be released into water systems, providing novel insights into the potential source of water-borne disinfectant-resistant pathogens.
水中出现对消毒剂耐药的病原体是对公众健康的重大威胁。然而，人类食用的药物是否会诱导细菌对消毒剂产生耐药性仍不清楚。在此，将大肠杆菌暴露于12种抗抑郁药中，并测试了抗抑郁药诱导的氯霉素（CHL）耐药突变体对消毒剂的敏感性。使用全基因组测序、全局转录组测序和实时定量聚合酶链反应来阐明潜在机制。我们观察到，度洛西汀、氟西汀、阿米替林和舍曲林显著增加了大肠杆菌对CHL的突变频率，增幅为15至2948倍。产生的突变体使次氯酸钠、苯扎溴铵和三氯生的平均最低抑菌浓度（MIC）大致增加了2至8倍。一致地，marRAB和acrAB - tolC基因以及ABC转运蛋白基因（如yddA、yadG、yojI和mdlA）被触发，增加了消毒剂从细胞中的外排，而ompF受到抑制，减少了消毒剂进入细胞的渗透。此外，在突变体中观察到marR和acrR中发生DNA突变，这可能导致AcrAB - TolC泵的合成增加。这项研究表明，药物暴露可能产生对消毒剂耐药的细菌，这些细菌随后可能被释放到水系统中，为水传播的对消毒剂耐药病原体的潜在来源提供了新的见解。
