Zhao Yuanfan, Zhang Jin, Gui Yixin, Ji Guangzhen, Huang Xianhuai, Xie Fazhi, Shen Huiyan
Key Laboratory of Water Pollution Control and Wastewater Resource of Anhui Province, College of Environment and Energy Engineering, Anhui Jianzhu University, Hefei, China.
Key Laboratory of Water Pollution Control and Wastewater Resource of Anhui Province, College of Environment and Energy Engineering, Anhui Jianzhu University, Hefei, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Jan;287:110057. doi: 10.1016/j.cbpc.2024.110057. Epub 2024 Oct 22.
The presence of antibiotic residues in the aquatic environments poses great potential risks to the aquatic organisms, and even human health. Elucidating the interaction mechanisms between antibiotics and biomacromolecules is crucial for accurately assessing and preventing their potential risks. Therefore, the toxicity of three beta-lactam antibiotics on Escherichia coli (E. coli) was investigated by using the time-dependent toxicity microplate analysis method in this study. Then, molecular docking and molecular dynamics simulation technologies were used to elucidate the potential molecular interactions between β-lactam antibiotics and penicillin-binding proteins of E. coli, and their correlation with the physical and chemical behaviors observed in the physiological and biochemical experiments. The results show that three antibiotics exert inhibitory effects on E. coli cells by modifying their membrane permeability, and even more severe cell damage including rupture, wrinkling, adhesion, indentation, elongation and size alterations. But, toxic effect of the three antibiotics on E. coli varies, and toxicity order is followed by meropenem > cefoperazone > amoxicillin. Van der Waals forces play a vital role in the molecular interactions between the three antibiotics penicillin binding protein of E. coli and the sequence of binding free energy is consistent with the observed toxicity order. Shape compensation is the principal determinant for the binding of antibiotics to penicillin binding proteins, which pertains to the drug-induced alteration in the three-dimensional conformation of penicillin binding proteins.
水环境中抗生素残留的存在对水生生物甚至人类健康都构成了巨大的潜在风险。阐明抗生素与生物大分子之间的相互作用机制对于准确评估和预防其潜在风险至关重要。因此，本研究采用时间依赖性毒性微孔板分析法研究了三种β-内酰胺类抗生素对大肠杆菌的毒性。然后，利用分子对接和分子动力学模拟技术阐明了β-内酰胺类抗生素与大肠杆菌青霉素结合蛋白之间潜在的分子相互作用，以及它们与生理生化实验中观察到的物理化学行为的相关性。结果表明，三种抗生素通过改变大肠杆菌细胞膜通透性对其细胞产生抑制作用，甚至导致更严重的细胞损伤，包括破裂、起皱、黏附、凹陷、伸长和大小改变。但是，这三种抗生素对大肠杆菌的毒性作用各不相同，毒性顺序为美罗培南>头孢哌酮>阿莫西林。范德华力在三种抗生素与大肠杆菌青霉素结合蛋白的分子相互作用中起着至关重要的作用，结合自由能顺序与观察到的毒性顺序一致。形状互补是抗生素与青霉素结合蛋白结合的主要决定因素，这与药物诱导的青霉素结合蛋白三维构象改变有关。
