Wang Peiliang, Wang Hanqing, Qi Shengchun, Wang Wei, Lu Huijie
Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China.
Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang, 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou, Zhejiang, 310058, China.
Water Res. 2025 May 1;275:123206. doi: 10.1016/j.watres.2025.123206. Epub 2025 Jan 25.
The usage of quaternary ammonium compounds (QACs) as disinfectants has surged dramatically during the COVID-19 pandemic and thereafter. QACs can promote antimicrobial resistance, but the combined effects of QACs and antibiotics in driving resistance evolution were yet revealed. This study aimed to evaluate antibiotic resistance of wastewater microorganisms under coexposure to typical antibiotics and the most widely used QAC, dodecyl dimethyl benzyl ammonium chloride (DDBAC). DDBAC exhibited synergistic effects with multiple antibiotics (ampicillin, azithromycin, ciprofloxacin, kanamycin, polymyxin B) in enhancing activated sludge resistance by 1.53-6.67 folds, compared with antibiotics exposure alone. DDBAC-ampicillin coexposure enriched multidrug and aminoglycoside ARGs with relatively high horizontal gene transfer potential. The synergistic mechanism was further explored using sludge-isolated pathogenic E. coli. DDBAC at 1-10 mg/L alone did not induce notable resistance, but synergized with ampicillin on enhancing resistance by 6.56-22.90 folds. Based on mutation analysis and transcriptomics, DDBAC-enhanced resistance evolution was attributable to efflux pump upregulation, target modification, and inhibition of ATP synthesis (a less reported mechanism). Five DDBAC-induced, resistance-conferring mutant genes were highly enriched in globally collected E. coli strains from wastewater outflow (n = 537) than soil/sediments (n = 714, p < 0.05). Considering the strong adsorption and persistence of QACs, their coexistence with antibiotics poses elevated antimicrobial resistance risks, particularly in wastewater treatment systems with long solid retention time and sewage sludge applied farmland.
在新冠疫情期间及之后，季铵化合物（QACs）作为消毒剂的使用量急剧增加。QACs可促进抗菌药物耐药性，但QACs与抗生素共同作用对耐药性进化的影响尚未明确。本研究旨在评估典型抗生素与应用最广泛的QAC——十二烷基二甲基苄基氯化铵（DDBAC）共同作用下废水微生物的抗生素耐药性。与单独使用抗生素相比，DDBAC与多种抗生素（氨苄青霉素、阿奇霉素、环丙沙星、卡那霉素、多粘菌素B）协同作用，使活性污泥耐药性提高了1.53至6.67倍。DDBAC与氨苄青霉素共同作用使具有较高水平基因转移潜力的多药和氨基糖苷类抗生素耐药基因（ARGs）富集。利用污泥分离的致病性大肠杆菌进一步探究协同作用机制。单独使用1至10mg/L的DDBAC不会引起显著耐药性，但与氨苄青霉素协同作用可使耐药性提高6.56至22.90倍。基于突变分析和转录组学，DDBAC增强的耐药性进化归因于外排泵上调、靶点修饰和ATP合成抑制（一种较少报道的机制）。与土壤/沉积物（n = 714）相比，5个由DDBAC诱导的耐药突变基因在全球收集的废水排放口大肠杆菌菌株（n = 537）中高度富集（p < 0.05）。考虑到QACs具有较强的吸附性和持久性，它们与抗生素共存会增加抗菌药物耐药性风险，尤其是在固体停留时间长的废水处理系统以及施用污水污泥的农田中。
