Sun Haoyu, Zhang Yulian, Wang Jing, Ren Long-Fei, Tong Danqing, Wang Jiajun, Tang Liang
Key Laboratory of Organic Compound Pollution Control Engineering (MOE), School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
School of Environmental and Material Engineering, Yantai University, Yantai 264005, China.
Sci Total Environ. 2023 Sep 20;892:164343. doi: 10.1016/j.scitotenv.2023.164343. Epub 2023 May 25.
Polypeptide antibiotics (PPAs), silver nanoparticles (plural) (AgNP) and quorum sensing inhibitors (QSIs) are considered to be the ideal antibiotic substitutes. Due to the great potential for the combined use of these antibacterial agents, it is necessary to evaluate their joint effects. In this study, the joint toxic actions for the binary mixtures of PPA + PPA, PPA + AgNP, and PPA + QSI were judged via the independent action (IA) model based on the individual and combined toxicity of test agents to the bioluminescence of Aliivibrio fischeri during 24 h. It was observed that the single agents (PPAs, AgNP, and QSI) and the binary mixtures (PPA + PPA, PPA + AgNP, and PPA + QSI) all triggered the time-dependent hormetic effects on the bioluminescence, where the maximum stimulatory rate, the median effective concentration, and the occurrence of hormesis varied with the increase of time. While bacitracin triggered the maximum stimulatory rate (266.98 % at 8 h) among the single agents, the mixture of capreomycin sulfate and 2-Pyrrolidinone induced the maximum stimulatory rate (262.21 % at 4 h) among the binary mixtures. The cross-phenomenon that the dose-response curve of mixture crossed the corresponding IA curve was observed in all treatments, which also varied with time, exhibiting that the joint toxic actions and corresponding intensities possessed dose- and time-dependent features. Furthermore, three kinds of binary mixtures resulted in three different variation tendencies for the time-dependent cross-phenomena. Mechanistic speculation indicated that test agents possessed the stimulatory modes of action (MOAs) at low-dose and inhibitory MOAs at high-dose to induce the hormetic effects, and the interplays between these MOAs varied with time to trigger the time-dependent cross-phenomenon. This study provides the reference data for the joint effects of PPAs and typical antibacterial agents, which will benefit the application of hormesis in the exploration of time-dependent cross-phenomenon and promote the future development of environmental risk assessment of pollutant mixtures.
多肽抗生素（PPAs）、银纳米颗粒（AgNP）和群体感应抑制剂（QSIs）被认为是理想的抗生素替代品。由于这些抗菌剂联合使用具有巨大潜力，因此有必要评估它们的联合效应。在本研究中，基于测试剂在24小时内对费氏弧菌生物发光的个体毒性和联合毒性，通过独立作用（IA）模型判断PPA + PPA、PPA + AgNP和PPA + QSI二元混合物的联合毒性作用。观察到单一药剂（PPAs、AgNP和QSI）以及二元混合物（PPA + PPA、PPA + AgNP和PPA + QSI）均对生物发光产生了时间依赖性的兴奋效应，其中最大刺激率、半数有效浓度以及兴奋效应的出现情况随时间增加而变化。在单一药剂中，杆菌肽引发的最大刺激率最高（8小时时为266.98%），而在二元混合物中，硫酸卷曲霉素和2-吡咯烷酮的混合物引发的最大刺激率最高（4小时时为262.21%）。在所有处理中均观察到混合物的剂量-反应曲线与相应IA曲线交叉的交叉现象，且该现象也随时间变化，表明联合毒性作用及其相应强度具有剂量和时间依赖性特征。此外，三种二元混合物导致时间依赖性交叉现象呈现出三种不同的变化趋势。机理推测表明，测试剂在低剂量时具有刺激作用模式（MOAs），在高剂量时具有抑制作用模式，从而诱导兴奋效应，并且这些作用模式之间的相互作用随时间变化，引发了时间依赖性交叉现象。本研究为PPAs与典型抗菌剂的联合效应提供了参考数据，这将有助于兴奋效应在时间依赖性交叉现象探索中的应用，并促进未来污染物混合物环境风险评估的发展。
