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Resistance risk induced by quorum sensing inhibitors and their combined use with antibiotics: mechanism and its relationship with toxicity
Chemosphere ( IF 8.8 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.chemosphere.2020.129153
Xufei Li , Yingying Liu , Yajuan Wang , Zhifen Lin , Dali Wang , Haoyu Sun

The abuse of antibiotics has brought out serious bacterial resistance, which threatens the ecological environment and human health. Quorum sensing inhibitors (QSIs), as a new kind of potential antibiotic substitutes that are theoretically difficult to trigger bacterial resistance, are recommended to individually use or jointly use with traditional antibiotics. However, there are few studies on the resistance risk in the use of QSIs. In this study, the influence of QSIs alone or in combination with sulfonamides (SAs) on conjugative transfer and mutation of Escherichia coli (E. coli) was investigated to explore whether QSIs have the potential to induce bacterial resistance. The results show that QSIs may facilitate plasmid RP4 conjugative transfer by binding with SdiA protein to regulate pilus expression, and interact with LsrR protein to increase SOS gene expression, inducing gene mutation. The QSIs-SAs mixtures could promote plasmid RP4 conjugative transfer and mutation in E. coli, and the main joint effects are synergism and antagonism. Furthermore, there is a good correlation among conjugative transfer, mutation, and growth inhibition of QSIs-SAs to E. coli. It could be speculated that bacteria may delay cell division to provide sufficient energy and time for regulating conjugative transfer and mutation under the stress of QSIs and their combined exposure with antibiotics, which is essentially a balance between bacterial resistance and toxicity. This study provides a reference for the resistance risk assessment of QSIs and benefits the clinical application of QSIs.



中文翻译:

群体感应抑制剂诱导的耐药风险及其与抗生素并用的机理及其与毒性的关系

滥用抗生素带来了严重的细菌耐药性,威胁到生态环境和人类健康。群体感应抑制剂(QSI)作为一种新型的潜在抗生素替代品,理论上难以触发细菌耐药性,建议单独使用或与传统抗生素联合使用。但是,关于使用QSI的抗药性风险的研究很少。在这项研究中,单独的QSI或与磺酰胺(SAs)结合使用的QSI对大肠杆菌E. coli)的共轭转移和突变的影响)进行了调查,以探讨QSI是否具有诱导细菌耐药性的潜力。结果表明,QSIs通过与SdiA蛋白结合调节菌毛表达,并与LsrR蛋白相互作用增加SOS基因表达,诱导基因突变,可以促进质粒RP4共轭转移。QSIs-SAs混合物可促进质粒RP4在大肠杆菌中的共轭转移和突变,其主要的联合作用是协同作用和拮抗作用。此外,QSIs-SAs向大肠杆菌的共轭转移,突变和生长抑制之间有良好的相关性。可以推测,细菌可能会延迟细胞分裂,以提供足够的能量和时间来调节QSIs以及它们与抗生素的联合暴露下的共轭转移和突变,这实质上是细菌耐药性和毒性之间的平衡。本研究为QSIs的抗药性风险评估提供参考,有利于QSIs的临床应用。

更新日期:2020-12-01
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