Abstract：
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 MIC50 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.
摘要：
水中耐消毒剂病原体的出现是对公众健康的主要威胁。然而,人类消耗的药物是否会引起细菌对消毒剂的耐药性尚不清楚。在这里，大肠杆菌暴露于12种抗抑郁药，并测试了抗抑郁剂诱导的氯霉素（CHL）抗性突变体对消毒剂的敏感性。全基因组测序，全局转录组测序，和实时定量聚合酶链反应用于阐明潜在的机制。我们观察到度洛西汀,氟西汀,阿米替林,和舍曲林使大肠杆菌对CHL的突变频率显著增加了15至2948倍。所得突变体增加了次氯酸钠的平均MIC50，苯扎溴铵,和三氯生大约2到8倍。始终如一，marRAB和acrAB-tolC基因，与ABC转运蛋白基因一起(例如，ydda,YadG,yoji,和MDLA)，被触发以增加消毒剂从细胞中流出，而ompF被抑制，减少消毒剂渗入细胞。此外,观察到突变体中MarR和acrR的DNA突变的发生，可能导致AcrAB-TolC泵的合成增加。这项研究表明，药物暴露可能会产生耐消毒剂的细菌，然后可以释放到水系统中，提供对水性消毒剂抗性病原体的潜在来源的新见解。
