Li Xi, Yu Zhigang, Ye Jiaqing, Wang Xiaolong, Lin Huai, Lei Liusheng, Hu Wenjin, Luo Yi
State Key Laboratory of Water Pollution Control and Green Resource Recycling, School of the Environment, Nanjing University, Nanjing 210093, China.
Australian Centre for Water and Environmental Biotechnology, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
Environ Sci Technol. 2025 Jul 1;59(25):12472-12484. doi: 10.1021/acs.est.4c13071. Epub 2025 Jun 16.
Numerous disinfectants have been discharged into the environment through anthropogenic activities, leading to ubiquitous coexistence of multiple disinfectants in the real environment. Previous studies reported that individual disinfectants induce the emergence of antimicrobial resistance (AMR); however, the impacts of the coexposure to multiple disinfectants on the development of AMR and its toxicity associated with bacterial pathogenicity are still unclear. Here, we conducted a 30-day stepwise exposure experiment to investigate the impacts of the commonly used disinfectants polyhexamethylene guanidine (PHMG), benzalkonium chloride (BAC), and their combination on AMR and pathogenicity of Wild-Type . Results reveal that the coexistence of dual disinfectants dramatically led to higher levels of AMR (2.0- to 14.8-fold) and pathogenicity (8.7-fold) in the evolved strains. Dual disinfectant-induced bacterial evolution is primarily driven by the alteration in the expression of key functional genes, such as those involved in biofilm formation and cell motility. In contrast, genetic mutations may not account for the increased AMR and pathogenicity in combination of dual disinfectant treatment, as similar gene mutations are responsible for both dual and single disinfectant stress. The evolved strains induced by disinfectant combination, characterized with transcriptional regulation, exhibited a synergistic or additive response on AMR and pathogenicity, which was further confirmed by a toxicology prediction model. This study demonstrated that dual disinfectants synergistically enhanced AMR and the associated pathogenicity, advancing our understanding of the risks posed by coexistence of multiple chemical pollutants in the environment.
众多消毒剂通过人为活动被排放到环境中，导致多种消毒剂在实际环境中普遍共存。先前的研究报道，单一消毒剂会促使抗菌药物耐药性（AMR）的出现；然而，同时接触多种消毒剂对AMR发展及其与细菌致病性相关毒性的影响仍不清楚。在此，我们进行了一项为期30天的逐步暴露实验，以研究常用消毒剂聚六亚甲基胍（PHMG）、苯扎氯铵（BAC）及其组合对野生型菌株的AMR和致病性的影响。结果显示，两种消毒剂共存显著导致进化菌株中更高水平的AMR（2.0至14.8倍）和致病性（8.7倍）。两种消毒剂诱导的细菌进化主要由关键功能基因表达的改变驱动，例如参与生物膜形成和细胞运动的基因。相比之下，基因突变可能不是两种消毒剂联合处理中AMR和致病性增加的原因，因为相似的基因突变在单一消毒剂和两种消毒剂应激中均起作用。由消毒剂组合诱导的进化菌株具有转录调控特征，在AMR和致病性方面表现出协同或相加反应，这通过毒理学预测模型得到进一步证实。本研究表明，两种消毒剂协同增强了AMR及相关致病性，增进了我们对环境中多种化学污染物共存所带来风险的理解。
