A Quorum Sensing Signal-based Study For Effect And Prediction Model Of Antibiotors' Toxicity On Luminous Bacteria

Antibiotics as a broad-spectrum antimicrobial drugs are widely used in medical,animal husbandry,aquaculture and other fields.However,the range of distribution and concentration in the environment are increasing because of the abuse and unreasonable disposition wastes of antibiotics.On account of the low dose,persistence and a series of exposure characteristics of antibiotics,arise of antibiotic-resistant genes is a threat to the human living environment,and the demand for antibiotic substitutes is becoming increasingly urgent.With the introduction of antibiotic substitutes and their further development,such as the use of Quorum Sensing Inhibitor?QSIs?,as antibiotic substitutes or in combination with antibiotics for medical use,it is expected that QSIs will coexist with antibiotics in the environment.However,it is not clear for the current study that the single environmental effects and environmental ecological risk impact of QSIs as an alternative to antibioticsis.Vibrio fischeri as a light-emitting bacteria which living in the vast ocean,there is a corresponding distribution in the environment of the resulting bacterial quorum sensing signal molecules C6,C8,but so far,the study of the effects of C6,C8 to antibiotics on luminous is still rare.Crossover refers to the phenomenon of intersecting?one or more?between the dose-response curve according to single pollutant toxicity use existing predicted model and the dose-effect curve of the combined effect of pollutants by experiments,it provide a good basis for determining the type of compounds combination which has been extensively studied in recent years.However,the mechanism of cross-phenomenon is not clear so far.In this paper,Vibrio fischeri as the model organisms,and sulfonamides antibioticsSMP,quorum sensing inhibitor C30 and quorum sensing signal molecules C6,C8 were used to study the effect of C6,C8 on single and combined toxicity?0-24h?and its cross-effects based on the IA model of antibiotics and quorum sensing inhibitors.It was found that:?1?C6 inhibits the toxic effects of single and combined toxicity of SMP,C30 on the luminescent bacteria,because C6 binds to the Lux R protein and starts the expression of luxICDABEG,thereby promoting luminescence.?2?the toxic effect of low concentration of C8 on the single and combined toxicity of SMP,C30 on the luminescent bacteria was inhibited.The toxic effect of the high concentration of C8 on the single and combined toxicity of SMP,C30 was inhibited at 0-12 h,while promoted at13-24 h,this is because with the secretion of C6 itself increased,exogenous C8 will compete with C6 competition LuxR protein,so that reduce the stimulating effect of C6 on the luminous bacteria.?3?C6 make the cross-point of combination effect of SMP and C30 increase,and C8 make the cross-point of combination effect of SMP and C30 decreases,it is because C6?C8 belongs to LuxI/Lux R systems of the Vibrio fischeri,and C8 belongs to AinS/AinR system.C6 play a role in the quorum sensing system before C8,and C8 is a large part of the supplement role combine with Lux R when C6 concentration insufficient.As C6 has a tendency to antagonize the co-toxicity of SMP+C30,whereas C8 has a tendency to synergy the co-toxicity of SMP+C30.In addition,the study of chronic toxicity is vital in the face of the complex,diverse exposure of today's pollutants.However,the current research on acute and chronic toxicity prediction models is mostly the choice of experience,lack of the mechanism of comparison theoretical basis.In this paper,we use the E_binding of LitR protein fitting with Ka/Kc to establish a QSAR model of chronic toxicity of different compounds from acute toxicity.The study found that there is a good correlation between LitR and target protein,which makes it possible to use LitR' E_binding instead of target protein' E_binding to fit with logKc/Ka.The results of this study not only provide theoretical basis for the assessment of ecotoxicological and antimicrobial agents,but also provide data support and theoretical guidance for the further exploration of the mechanism of cross phenomenon formation.