State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
College of Marine Ecology and Environment, Shanghai Ocean University, Shanghai, 201306, China.
Ecotoxicol Environ Saf. 2020 Dec 1;205:111300. doi: 10.1016/j.ecoenv.2020.111300. Epub 2020 Sep 19.
Bacterial resistance caused by the abuse of antibiotics has attracted worldwide attention. However, there are few studies exploring bacterial resistance under the environmental exposure condition of antibiotics that is featured by low-dose and mixture. In this study, sulfonamides (SAs), sulfonamide potentiators (SAPs) and tetracyclines (TCs) were used to determine the effects of antibiotics on plasmid RP4 conjugative transfer of Escherichia coli (E. coli) under single or combined exposure, and the relationship between the effects of antibiotics on conjugative transfer and growth was investigated. The results show that the effects of single or binary antibiotics on plasmid RP4 conjugative transfer all exhibit a hormetic phenomenon. The linear regression reveals that the concentrations of the three antibiotics promoting conjugative transfer are correlated with the concentrations promoting growth and the physicochemical properties of the compounds. The combined effects of SAs-SAPs and SAs-TCs on plasmid conjugative transfer are mainly synergistic and antagonistic. While SAPs provide more effective concentrations for the promotion of conjugative transfer in SAs-SAPs mixtures, SAs play a more important role in promoting conjugative transfer in SAs-TCs mixtures. Mechanism explanation shows that SAs, SAPs and TCs inhibit bacterial growth by acting on their target proteins DHPS, DHFR and 30S ribosomal subunit, respectively. This study indicates that toxic stress stimulates the occurrence of conjugative transfer and promotes the development of bacterial resistance, which will provide a reference for resistance risk assessment of antibiotic exposure.
抗生素滥用导致的细菌耐药性问题已引起全球关注。然而，目前关于抗生素在低剂量和混合暴露环境下导致细菌耐药性的研究较少。本研究采用磺胺类药物（SAs）、磺胺增效剂（SAPs）和四环素类药物（TCs），研究了单一或联合暴露条件下抗生素对大肠杆菌（E. coli）RP4 质粒接合转移的影响，并探讨了抗生素对接合转移的影响与生长之间的关系。结果表明，单一或二元抗生素对质粒 RP4 接合转移的影响均呈现出一种兴奋效应。线性回归表明，三种抗生素促进接合转移的浓度与促进生长的浓度以及化合物的物理化学性质相关。SAs-SAPs 和 SAs-TCs 对质粒接合转移的联合效应主要为协同和拮抗。SAs-SAPs 混合物中 SAPs 提供了更有效的促进接合转移的浓度，而 SAs-TCs 混合物中 SAs 则在促进接合转移方面发挥了更重要的作用。机制解释表明，SAs、SAPs 和 TCs 分别通过作用于 DHPS、DHFR 和 30S 核糖体亚基来抑制细菌生长。本研究表明，毒性应激刺激了接合转移的发生，促进了细菌耐药性的发展，这将为抗生素暴露的耐药性风险评估提供参考。
