Wang Dali, Lin Zhifen, Huo Zhengyang, Wang Ting, Yao Zhifeng, Cong Yongping
State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
Collaborative Innovation Center for Regional Environmental Quality, Beijing, China.
Bull Environ Contam Toxicol. 2016 Jul;97(1):145-50. doi: 10.1007/s00128-016-1801-z. Epub 2016 Apr 15.
Quorum sensing inhibitors (QSIs) are a promising alternative to the antibiotics and unlikely to induce drug resistance. However, toxicity studies on the QSIs remain limited; therefore in this paper we investigated the acute (15 min) and chronic (24 h) toxicity of some potential QSIs on both gram-negative (V. fischeri) and gram-positive bacteria (B. subtilis). It was found that the toxicity of the QSIs differed with the toxicity test periods. QSAR models were developed for both the acute and chronic toxicity, using the interaction energies between QSIs and the relevant proteins, and the frontier orbital energies. Based on the QSAR models, it was suggested that QSIs primarily bind with the luciferase at 15 min, but LuxR at 24 h in V. fischeri; whereas in B. subtilis, the QSIs mainly bind with LuxS. Our study provided an insight into the toxicity mechanism for QSIs during different exposure periods.
群体感应抑制剂（QSIs）是抗生素的一种有前景的替代品，且不太可能诱导耐药性。然而，关于QSIs的毒性研究仍然有限；因此，在本文中，我们研究了一些潜在的QSIs对革兰氏阴性菌（费氏弧菌）和革兰氏阳性菌（枯草芽孢杆菌）的急性（15分钟）和慢性（24小时）毒性。结果发现，QSIs的毒性因毒性测试周期而异。利用QSIs与相关蛋白质之间的相互作用能以及前沿轨道能，建立了急性和慢性毒性的定量构效关系（QSAR）模型。基于QSAR模型，表明在费氏弧菌中，QSIs在15分钟时主要与荧光素酶结合，但在24小时时与LuxR结合；而在枯草芽孢杆菌中，QSIs主要与LuxS结合。我们的研究深入了解了QSIs在不同暴露时期的毒性机制。
