[en] 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.