Antidepressant exposure as a source of disinfectant resistance in waterborne bacteria

• Published in: Journal of hazardous materials 2023-06, Vol.452, p.131371-131371, Article 131371
• Main Authors: Li, Haibei, Li, Xinmei, Chen, Tianjiao, Yang, Zhongwei, Shi, Danyang, Yin, Jing, Yang, Dong, Zhou, Shuqing, Li, Junwen, Jin, Min
• Format: Article
• Language: English
• Subjects: ABC transporter genes; acrAB-tolC; Anti-Bacterial Agents - pharmacology; Antidepressants; Antidepressive Agents; Disinfectant resistance; Disinfectants - toxicity; Escherichia coli; Escherichia coli - genetics; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2023.131371

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. [Display omitted] •Four antidepressants induced the emergency of CHL-resistant E. coli mutants.•The E. coli mutants displayed increased tolerance to disinfectants.•Mutations in marR and acrR genes were observed in E. coli mutants.•The mutants withstood NaClO through altering efflux and porin gene expression.