抗生素单一及联合暴露对RP4质粒介导的抗性基因水平转移的hormesis效应研究

抗生素滥用导致的抗性基因(ARGs)泛滥问题引起人们的日益关注。目前关于抗性基因的研究主要集中在环境监测方面,但是关于抗生素对ARGs传播的影响研究还相对缺乏。质粒是ARGs传播的重要载体,因此以基于RP4质粒的大肠杆菌(E.coli)接合转移体系为研究对象,探讨了盐酸四环素、甲氧苄啶、磺胺氯哒嗪、磺胺异唑在单一暴露条件下对RP4质粒接合转移的影响。根据单一暴露的结果设计混合抗生素的浓度比,探究抗生素联合暴露实验对质粒接合转移的影响。结果表明:在单一暴露条件下,只有盐酸四环素对含有四环素抗性的RP4质粒的接合转移频率有低促高抑的hormesis效应;在联合暴露条件下,对RP4质粒接合转移无促进作用的抗生素会抑制四环素的hormesis效应,这一定程度上降低了抗生素的环境风险。并且用受体理论解释了抗生素对质粒接合转移的hormesis效应产生机制,为目前尚无定论的hormesis受体理论机制提供了证据支持。

Hormesis Effect of Single and Combined Exposure of Antibiotics on Antibiotic Resistance Gene Transfer Mediated by RP4 Plasmid

The abuse of antibiotics has caused a series of environmental problems, among which the antibiotic resistance genes (ARGs) problem is the most concerned. However, the majority of the current researches mainly focused on the environmental monitoring of the antibiotics and ARGs, while researches about the influence of antibiotics on the transfer of ARGs is still lacking. In this study, the frequency of RP4 plasmid transfer was measured in co-cultures of a donor and an acceptor strain upon exposure to tetracycline, trimethoprim, sulfachloropyridazine and sulfamethoxazole, both individually and in combination. The results revealed that the transfer frequency of RP4 plasmid that contained the tetracycline ARGs showed hormetic responses to the exposure of single tetracycline, which were inhibited when combined with other antibiotics. It is the first time that the receptor theory is used to explain the hormetic mechanism of the antibiotics on the plasmid conjugation transfer, and evidence is provided for the hormesis receptor theory that is not yet conclusive.