title: The joint effects of sulfonamides and quorum sensing inhibitors on Vibrio fischeri: Differences between the acute and chronic mixed toxicity mechanisms.
abstract: Quorum sensing inhibitors (QSIs) are considered to be promising antibiotic alternatives and will be increasingly exposed to the environment together with antibiotics after their research and development process; it is therefore necessary to study the joint effects of QSIs and antibiotics. In this study, single and mixed toxicity of sulfonamide (SAs) and QSIs under acute and chronic conditions and their corresponding toxicity mechanisms were investigated. The results indicated that the acute joint effect was extremely complex, ranging from an antagonistic to synergistic response, while the chronic joint effect was primarily an antagonistic response. Using a molecular docking and regression model, we found that the acute joint effect could be determined by the hydrion's, ability to be oxidized, as well as the binding energy. The chronic joint effect was primarily an antagonistic response, which was due to the QSI competing against AHL for luxR generated by SAs, leading to negative effects of the QSI-luxR complexes on luxI. This phenomenon eventually weakened the stimulatory effect caused by SAs. Finally, the main differences between acute and chronic mixtures were analyzed: (1) The target protein was different between acute and chronic toxicity mixtures, and (2) effective concentration in acute and chronic toxicity mixtures was also different. These deep insights into mixed toxicity mechanisms will play an important role in the study of antibiotic resistance genes in response to antibiotic replacements.
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: Yuewei
authors.initials: Y
authors.lastname: Liu
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 Substainability, 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. Electronic address: csyin@shou.edu.cn.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Yin
authors.affiliation: Collaborative Innovation Center for Regional Environmental Quality, Beijing, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001426:Bacterial Proteins / Q000378:metabolism; D008958:Models, Molecular; D053038:Quorum Sensing / Q000187:drug effects*; D012097:Repressor Proteins / Q000378:metabolism; D013449:Sulfonamides / Q000633:toxicity*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012097:Repressor Proteins; D013449:Sulfonamides; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins
keywords: Acute toxicity; Chronic toxicity; Quorum sensing inhibitors; Sulfonamide; Toxicity mechanisms