Suominen Eetu N, Putus Tuula, Atosuo Janne
The Department of Biochemistry, Faculty of Science and Engineering, University of Turku, Finland.
Department of Occupational and Environmental Health, Faculty of Medicine, University of Turku, Finland.
Heliyon. 2020 Jul 2;6(7):e04232. doi: 10.1016/j.heliyon.2020.e04232. eCollection 2020 Jul.
We have previously established that the -lux assessment is a convenient tool for rapid measurements of the kinetical features of short-term toxicity caused by various factors. In this study, kinetic measurements of seven specifically acting model antibacterials (i.e., polymyxin B, chloramphenicol, nalidixic acid, kanamycin, deoxynivalenol, erythromycin and tetracycline) and two metals (AgNO and CdCl) against -lux through a bioluminescence- and optical density-based real-time assay that combined short- and long-term toxicity assessments were performed. Bacteria were exposed to antibacterials and the effects were reported as the half-maximum effective concentration (EC) after 30 min and 10 h. Regarding the 10-hour endpoints, all reference compounds, except deoxynivalenol, showed dose-response inhibition in the studied concentration range. The analysis of chloramphenicol, kanamycin, erythromycin, tetracycline and nalidixic acid clearly revealed the limitations of short-term inhibition tests. No significant differences were observed between the results obtained from luminescence inhibition and growth inhibition assays. The kinetical data from measurements provide differentiation between bacteriostatic and bactericidal mechanisms of various types of antibacterial agents. The combined assessment of short- and long-term effects reduces the risk of the underestimation of toxicity due to an inaccurate endpoint selection. The cost-efficient and fully automated -lux assessment technique may offer possibilities for high-throughput screening procedures.
我们之前已经确定，-lux评估是一种便捷工具，可用于快速测量由各种因素引起的短期毒性的动力学特征。在本研究中，通过基于生物发光和光密度的实时测定法，结合短期和长期毒性评估，对七种特异性作用的模型抗菌剂（即多粘菌素B、氯霉素、萘啶酸、卡那霉素、脱氧雪腐镰刀菌烯醇、红霉素和四环素）和两种金属（硝酸银和氯化镉）对-lux的动力学进行了测量。将细菌暴露于抗菌剂中，并将30分钟和10小时后的效应报告为半数最大效应浓度（EC）。关于10小时的终点，除脱氧雪腐镰刀菌烯醇外，所有参考化合物在研究浓度范围内均显示出剂量反应抑制。氯霉素、卡那霉素、红霉素、四环素和萘啶酸的分析清楚地揭示了短期抑制试验的局限性。发光抑制试验和生长抑制试验的结果之间未观察到显著差异。测量得到的动力学数据可区分各种类型抗菌剂的抑菌和杀菌机制。短期和长期效应的联合评估降低了由于终点选择不准确而低估毒性的风险。这种经济高效且完全自动化的-lux评估技术可能为高通量筛选程序提供可能性。
