title: Prediction of mixture toxicity from the hormesis of a single chemical: A case study of combinations of antibiotics and quorum-sensing inhibitors with gram-negative bacteria.
abstract: The 50% effect level of a single chemical in the real environment is almost impossible to determine at the low exposure concentration, and the prediction of the concentration of a mixture at the 50% effect level from the concentration of a single chemical at the low effect level is even more difficult. The current literature does not address this problem. Thus, to determine solutions for this question, single/mixture chronic toxicities of sulfonamides (SAs) and quorum-sensing inhibitors (QSIs) were determined using Gram-negative bacteria (Vibrio fischeri and E. coli.) and Gram-positive bacteria (B. subtilis) as the target organisms. The results showed that the joint effects of SAs and QSIs were primarily antagonistic responses. In addition, the toxicity mechanisms of mixtures of SAs and QSIs were investigated further, and the results revealed that the chronic joint effects were primarily an antagonistic response due to the QSI competing against acyl-homoserine lactones (AHL) for luxR in V. fischeri and SdiA in E. coli generated by the SAs, leading to negative effects exerted by the QSI-luxR or QSI-SdiA complexes on luxI in V. fischeri or FtsZ in E. coli. This phenomenon eventually weakened the stimulatory effect caused by the SAs. Based on the mixture toxicity mechanism, the relationship between the mixture toxicity and the simulation effect was formulated.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Key Lab of Chemical Assessment and Sustainability, Shanghai, China; Collaborative Innovation Center for Regional Environmental Quality, Beijing, China. Electronic address: lzhifen@tongji.edu.cn.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Lin
authors.affiliation: College of Marine Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: An
authors.affiliation: College of Marine Science, Shanghai Ocean University, Shanghai 201306, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Yin
authors.affiliation: Shanghai Key Lab of Chemical Assessment and Sustainability, Shanghai, China.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Huang
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000633:toxicity*; D001412:Bacillus subtilis / Q000187:drug effects; D001426:Bacterial Proteins / Q000737:chemistry; D004336:Drug Antagonism; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D059165:Hormesis / Q000187:drug effects*; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D053038:Quorum Sensing / Q000187:drug effects*; D013449:Sulfonamides / Q000737:chemistry / Q000633:toxicity*; D036401:Toxicity Tests, Chronic; D015534:Trans-Activators / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004785:Environmental Pollutants; D013449:Sulfonamides; D015534:Trans-Activators
keywords: Antibiotics; Hormesis; Mixture toxicity; Quorum sensing inhibitors; Toxicity mechanism