摘要   

      抗生素耐药基因（ARGs）是一类新兴的环境污染物，对全球公共健康构成了巨大威胁。虽然人们对ARGs的污染进行了广泛的研究，但在探讨抗生素对ARGs的产生和传播的影响时，对其结构信息的关注甚少。本研究以大肠杆菌（E.coli）为试验菌，研究了磺胺类药物（SAs）对大肠杆菌生长、突变频率和结合转移频率的影响，并利用定量构效关系（QSAR）定量分析SAs对这些生物效应的促进作用，探讨其可能机制。所构建的QSAR模型表明，SAs可能通过与SdiA蛋白的结合增加FtsZ蛋白和pili在大肠杆菌中的表达，最终导致SAs促进生长、突变频率和结合转移频率。结果表明，SAs能对大肠杆菌产生选择性压力，促进ARGs的产生和传播。本研究为进一步研究抗生素暴露下ARGs的产生和传播提供了参考数据，为ARG污染的机理探索提供了新的视角。

        Antibiotic resistance genes (ARGs), which are emerging environmental contaminants, have posed great threats to global public health. Although extensive efforts have been undertaken to investigate ARG pollution, little attention has been paid to the structural information of antibiotics when exploring their impact on the emergence and dissemination of ARGs. In this study, setting Escherichia coli (E. coli) as the test organism, the effects of sulfonamides (SAs) on growth, mutation frequency and conjugative transfer frequency were tested, and quantitative structure-activity relationship (QSAR) was used to quantitatively analyze the promotion of SAs on these biological effects and explore their possible mechanism. The constructed QSAR models reveal that SAs may increase expression of the FtsZ protein and pili in E. coli via binding to the SdiA protein, ultimately leading to SAs facilitation of growth, mutation frequency and conjugative transfer frequency. The results indicate that SAs can produce selective pressure on E. coli to promote the emergence and dissemination of ARGs. This study provides reference data for further investigation of the emergence and dissemination of ARGs under antibiotic exposure and a new perspective for the mechanistic exploration of ARG pollution.

         https://www.sciencedirect.com/science/article/abs/pii/S0013935119301483?via%3Dihub