Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 511443, China.
Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 511443, China; Department of Environmental Science, Institute of Biomedical Studies, Baylor University, Waco, TX, USA.
Environ Pollut. 2020 Jul;262:114275. doi: 10.1016/j.envpol.2020.114275. Epub 2020 Feb 27.
Antibiotics in the environment usually co-exist with their transformation products with retained toxicity, raising concerns about environmental risks of their combined exposure. Herein, we reported a novel predictive approach for evaluating the individual and combined toxicity for photodegradation products of fluoroquinolone antibiotics (FQs). Quantitative structure-activity relationship (QSAR) models with promising predictive performance were constructed and validated using experimental data obtained with 13 FQs and 78 mixtures towards E. coli. A structural descriptor reflecting the interaction among FQ molecules and the target protein was employed in the QSAR models, which was obtained through molecular docking and thus provided a rational mechanistic explanation for these models. The predicted results indicated that the degradation products displayed varying degrees of changes compared to the parent FQs, while the combined toxicity of FQs and their degradation products was mostly additive. Furthermore, following UV irradiation the degradation products displayed elevated capacity of inducing resistance mutations in E. coli, though their overall toxicity was reduced. This result highlights the implications of antibiotic degradation products on resistance development in bacteria and stresses the importance of considering such impacts during environmental risk assessments of antibiotics.
环境中的抗生素通常与具有保留毒性的转化产物共存，这引起了人们对其联合暴露的环境风险的关注。在此，我们报道了一种用于评估氟喹诺酮类抗生素（FQs）光降解产物的单独和联合毒性的新型预测方法。使用 13 种 FQs 和 78 种混合物对大肠杆菌进行实验，构建并验证了具有良好预测性能的定量构效关系（QSAR）模型。QSAR 模型中使用了一个反映 FQ 分子与目标蛋白之间相互作用的结构描述符，该描述符是通过分子对接获得的，从而为这些模型提供了合理的机制解释。预测结果表明，与母体 FQs 相比，降解产物表现出不同程度的变化，而 FQs 及其降解产物的联合毒性大多是相加的。此外，经紫外线照射后，降解产物在大肠杆菌中诱导耐药突变的能力增强，尽管其整体毒性降低。这一结果强调了抗生素降解产物对细菌耐药性发展的影响，并强调了在抗生素环境风险评估中考虑此类影响的重要性。
