Key Laboratory of Organic Compound Pollution Control Engineering (MOE), School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
J Hazard Mater. 2024 Nov 5;479:135767. doi: 10.1016/j.jhazmat.2024.135767. Epub 2024 Sep 6.
Antibiotics usually induce the hormetic effects on bacteria, featured by low-dose stimulation and high-dose inhibition, which challenges the central belief in toxicity assessment and environmental risk assessment of antibiotics. However, there are currently no ideal parameters to quantitatively characterize hormesis. In this study, an effective area in hormesis (A) was developed to quantify the biphasic dose-responses of single antibiotics (sulfonamides (SAs), sulfonamides potentiators (SAPs), and tetracyclines (TCs)) and binary mixtures (SAs-SAPs, SAs-TCs, and SAs-SAs) to the bioluminescence of Aliivibrio fischeri. Using E (the lowest interaction energy between antibiotic and target protein) and K (octanol-water partition coefficient) as the structural descriptors, the reliable quantitative structure-activity relationship (QSAR) models were constructed for the A values of test antibiotics and mixtures. Furthermore, a novel method based on A was established to judge the joint toxic actions of binary antibiotics, which mainly exhibited synergism. The results also indicated that SAPs (or TCs) contributed more than SAs in the hormetic effects of antibiotic mixtures. This study proposes a new quantitative parameter for characterizing and predicting antibiotic hormesis, and considers hormesis as an integrated whole to reveal the combined effects of antibiotics, which will promote the development of risk evaluation for antibiotics and their mixtures.
抗生素通常对细菌产生激效作用，表现为低剂量刺激和高剂量抑制，这对抗生素毒性评估和环境风险评估的核心信念提出了挑战。然而，目前还没有理想的参数来定量描述激效。在本研究中，开发了一个有效的激效区（A），用于量化单一抗生素（磺胺类药物（SAs）、磺胺增效剂（SAPs）和四环素类（TCs））和二元混合物（SAs-SAPs、SAs-TCs 和 SAs-SAs）对发光菌（Aliivibrio fischeri）生物发光的双相剂量反应。使用 E（抗生素与靶蛋白之间的最低相互作用能）和 K（辛醇-水分配系数）作为结构描述符，构建了测试抗生素和混合物的 A 值的可靠定量构效关系（QSAR）模型。此外，还基于 A 建立了一种新的方法来判断二元抗生素的联合毒性作用，主要表现为协同作用。结果还表明，SAPs（或 TCs）在抗生素混合物的激效作用中比 SAs 贡献更大。本研究提出了一个新的定量参数来描述和预测抗生素的激效作用，并将激效作用视为一个整体，以揭示抗生素的联合作用，这将促进抗生素及其混合物风险评估的发展。
