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银系抗菌化合物、群体感应抑制剂及其二元混合物对大肠杆菌细菌耐药性的兴奋剂量反应。

Hormetic dose-responses for silver antibacterial compounds, quorum sensing inhibitors, and their binary mixtures on bacterial resistance of Escherichia coli.

机构信息

School of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China.

出版信息

Sci Total Environ. 2021 Sep 10;786:147464. doi: 10.1016/j.scitotenv.2021.147464. Epub 2021 May 1.

Abstract

Silver antibacterial compounds (SACs) and quorum sensing inhibitors (QSIs), as the potential antibiotic substitutes, have been recommended to prevent and treat microbial infections for the purpose of controlling the increasingly serious bacterial resistance induced by the abuse of antibiotics. However, there is little information regarding the resistance risk of these compounds, especially their mixtures. In this study, bacterial mutation and RP4 plasmid conjugative transfer among bacteria were used to characterize the bacterial endogenous and exogenous resistance, respectively. The effects of SACs (including silver nitrate (AgNO) and silver nanoparticle (AgNP)), QSIs, and their binary mixtures on the bacterial resistance were investigated via setting the frequency of mutation and conjugative transfer in Escherichia coli (E. coli) as the test endpoints. The results indicated that these two endpoints exhibited hormetic dose-responses to each treatment. Furthermore, the joint resistance actions between SACs and QSIs were all judged to be antagonism. Correlation analysis suggested that the promotion of the bacterial resistance in each treatment was closely related to its toxicity. It was speculated that AgNO and AgNP might both release Ag ions to facilitate the E. coli resistance, while QSIs probably acted on LsrR and SdiA proteins to stimulate the bacterial mutation and accelerate the RP4 plasmid conjugative transfer, respectively. These findings imply that the bacteria may generate targeted stress response to the survival pressure from environmental compounds, displaying hormetic phenomenon in resistance-related test endpoints. This study provides a new insight into the resistance risk induced by SACs and QSIs, benefiting the environmental risk assessment of these compounds from the perspective of bacterial resistance.

摘要

银系抗菌化合物(SACs)和群体感应抑制剂(QSIs)作为潜在的抗生素替代品,被推荐用于预防和治疗微生物感染,以控制抗生素滥用引起的日益严重的细菌耐药性。然而,关于这些化合物的耐药风险,尤其是它们的混合物的信息却很少。本研究采用细菌突变和 RP4 质粒接合转移分别表征了细菌的内源性和外源性耐药性。通过将大肠杆菌(E. coli)的突变和接合转移频率作为测试终点,研究了 SACs(包括硝酸银(AgNO)和银纳米颗粒(AgNP))、QSIs 及其二元混合物对细菌耐药性的影响。结果表明,这两个终点对每种处理均表现出兴奋剂量-反应关系。此外,SACs 和 QSIs 之间的联合耐药作用均被判定为拮抗作用。相关分析表明,每种处理中细菌耐药性的增强与其毒性密切相关。推测 AgNO 和 AgNP 可能均通过释放 Ag 离子来促进大肠杆菌耐药性,而 QSIs 可能分别作用于 LsrR 和 SdiA 蛋白来刺激细菌突变和加速 RP4 质粒接合转移。这些发现表明,细菌可能会对环境化合物的生存压力产生靶向应激反应,在与耐药性相关的测试终点表现出兴奋现象。本研究从细菌耐药性的角度为 SACs 和 QSIs 引起的耐药风险提供了新的见解,有利于这些化合物的环境风险评估。

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