混合抗生素对大肠杆菌耐药性的联合诱导效应

Combined Induction Effects of Quorum Sensing Inhibitors and Quinolones on Escherichia coli RP4 Plasmid Conjugative Transfer

群体感应抑制剂(quorum sensing inhibitors,QSIs)作为一类新型抗生素,具有广阔的应用前景,目前已被使用在水产养殖、污水治理和农作物病害防治等领域中,其与传统抗生素极有可能在环境中共存。因此,有必要探究QSIs与传统抗生素对细菌耐药性的联合效应。以往的研究往往采用单位法探究固定浓度下混合抗生素的联合耐药效应,但单位法无法在较大浓度范围评价其联合耐药风险。该研究以RP4质粒接合转移表征细菌耐药性的传播,将独立作用模型(independent action,IA)应用到联合耐药作用的判别中,以喹诺酮(quinolones,QNs)作为传统抗生素的代表,探究了QSIs与QNs对大肠杆菌(Escherichia coli)RP4质粒接合转移的联合效应。结果表明,15组QSIs-QNs混合物均能诱导E.coli产生接合转移效应,混合物的最大促进率在23.32%~73.07%。对比IA曲线与混合物对E.coli接合转移的剂量-效应曲线的位置关系,发现QSIs-QNs对E.coli的联合接合作用均表现出浓度依赖特征,即混合物促进E.coli接合转移频率时的联合作用模式随浓度增加由协同作用转变成拮抗作用。通过QSIs-QNs对E.coli的联合毒性实验,推测测试混合抗生素浓度依赖的联合接合作用与其联合毒性作用密切相关。该研究能够为今后探索QSIs与传统抗生素联合暴露的环境风险评估提供参考。

Quorum sensing inhibitors(QSIs),as new-typed antibiotics currently being used in the fields of aquaculture,sewage treatment,and crop disease control,have a wide application prospect.Since they are very likely to coexist with the traditional antibiotics in the environment,it is necessary to explore the joint effects of QSIs and the traditional antibiotics on bacterial resistance.Previous studies often use the unit method to explore the joint resistance effects of mixed antibiotics at a fixed concentration,but the unit method cannot evaluate the joint resistance risk in a wide range of the concentrations.In this study,the conjugative transfer of RP4 plasmid was used to characterize the spread of bacterial drug resistance,and the independent action model(IA)was applied to the discrimination of combined drug resistance,and with quinolones(QNs)as representatives of traditional antibiotics,the effects of QSIs and QNs on the combined effects of conjugative transfer of E.coli RP4 plasmids were investigated.As a result,the findings revealed that all the 15 groups of QSIs-QNs mixtures could induce the conjugative transfer effects of E.coli,and the maximum promoting rate of the mixture was in the range of 23.32%~73.07%;comparing the IA curve with the dose-effect curve of QSIs-QNs mixture of the E.coli conjugative transfer in terms of positional relationship,it was found that the combined conjugative effects of QSIs-QNs on E.coli presented a concentration-dependent feature,i.e.,when the mixture promoted the conjugative transfer frequency of E.coli,the joint action mode would change from synergistic effects to antagonistic effects with a increase of concentration;and through the joint experiment of toxicity to E.coli with QSIs-QNs,it was speculated that the concentration-dependent joint conjugative effects of the tested mixed antibiotics were closely related to its joint toxicity.Finally,it is expected that the achievements of the study could provide a reference for exploring the environmental risk assessment of combined exposure of QSIs and traditional antibiotics in the future.