Model of hormesis and its toxicity mechanism based on quorum sensing: a case study on the toxicity of sulfonamides to Photobacterium phosphoreum.
During the past two decades, the phenomenon of hormesis has gained increasing recognition in environmental and toxicological communities. However, the mechanistic understanding of hormesis, to date, is extremely limited. Herein is proposed a novel parametric model with a mechanistic basis and two model-based parameters for hormesis that was successfully applied to the hormetic dose-response observed in the chronic toxicity of sulfonamides on Photobacterium phosphoreum. On the basis of the methods of molecular docking and quantitative structure-activity relationships (QSARs), we proposed a mechanistic hypothesis for hormesis that introduces for the first time the concept of quorum sensing in toxicological studies and explains the mechanism at the level of the receptors. The mechanistic hypothesis stated that (1) specific target binding like interaction with LuxR may contribute to transcriptional activation leading to enhanced luciferase activity at low dose exposure of sulfonamides, and (2) as the dose of sulfonamides increases, more sulfonamides competitively bind to dihydropteroate synthase, which inhibit the biosynthesis of folic acid and thus provoke toxicity. This mechanistic hypothesis, which explains both the dose-dependent and time-dependent features of hormesis, could give new insight into the mechanistic study of hormesis.
State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
Ziqing
Z
Deng
Zhifen
Z
Lin
Xiaoming
X
Zou
Zhifeng
Z
Yao
Dayong
D
Tian
Dali
D
Wang
Daqiang
D
Yin
D001665:Binding Sites; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059165:Hormesis / Q000187:drug effects*; D008954:Models, Biological; D010776:Photobacterium / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D053038:Quorum Sensing / Q000187:drug effects*; D012097:Repressor Proteins / Q000378:metabolism; D013449:Sulfonamides / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests; D036401:Toxicity Tests, Chronic; D015534:Trans-Activators / Q000378:metabolism
D002373:Cyclic AMP Receptor Protein; D012097:Repressor Proteins; D013449:Sulfonamides; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins