| Since antibacterial agents’discovery,antibacterial agents have been widely used in human health care and animal husbandry because of their good anti pathogen effect.Due to the large use and continuous emission of antibacterial agents,antibacterial agents remain in the environment.Antibacterial agents have become a new kind of pollutants that can not be ignored.Due to the wide variety of antimicrobial agents,they are usually exposed in the environment.It is particularly important to study their combined toxic effects and evaluate the pollution ecological risk of antimicrobial agents.In addition,the resistance genes produced by bacteria induced by antibacterial agents will also remain in the environment for a long time,which is more harmful to the environment than the antibacterial agent itself.Therefore,while studying the toxic effects of antimicrobial agents,the effects of antimicrobial agents on their resistance genes also need to be paid attention to.Based on this,this paper studied the toxicity and mutagenic effects of two kinds of typical traditional antibacterial agents——aminoglycoside antibacterial agents（neomycin sulfate,streptomycin sulfate,gentamicin sulfate）,β-lactam antibacterial agents（amoxicillin trihydrate,cefotaxime Na,oxacillin sodium）and quorum sensing inhibitors（2（5H）-Furanone,2,5-Di Methyl-4-hydroxy-3（2H）-furanone,4-Acetoxy-2,5-Di Methyl-3-furanone,2-Methyltetrahydrofuran-3-one,Benzofuran-3（2H）-one）on Escherichia coli.The results are as follows:1)Aminoglycoside antibacterial agents,β-Lactam antibacterial agents and quorum sensing inhibitors significantly inhibited the growth of Escherichia coli,and the dose-response curves showed hormesis effect of low concentration promotion and high concentration inhibition;The toxicity to Escherichia coli(log(1/EC50))were 5.725mol·L-1（neomycin sulfate）,5.268 mol·L-1（streptomycin sulfate）,4.833 mol·L-1（gentamicin sulfate）,5.43 mol·L-1（amoxicillin trihydrate）,4.654 mol·L-1（cefotaxime sodium）,3.47 mol·L-1（oxacillin sodium）,1.612 mol·L-1（2（5H）-furanone）1.584mol·L-1（2,5-dimethyl-4-hydroxy-3（2H）-furanone）,1.831 mol·L-1（4-acetoxy-2,5-dimethyl-3-furanone）,1.09 mol·L-1（2-methyltetrahydrofuran-3-one）and1.549 mol·L-1（3-benzofuranone）,The order of single toxicity of 11 tested compounds to Escherichia coli was neomycin sulfate>amoxicillin trihydrate>streptomycin sulfate>gentamicin sulfate>cefotaxime sodium>oxacillin sodium>4-acetoxy-2,5-dimethyl-3-furanone>2（5H）-furanone>2,5-dimethyl-4-hydroxy-3（2H）-furanone>3-benzofuranone>2-methyltetrahydrofuran-3-one;Combined toxic effect of aminoglycoside antibacterial agent and quorum sensing inhibitor on Escherichia coli and the combined toxic effects of the mixed system ofβ-lactam antibacterial agents and quorum sensing inhibitors on Escherichia coli are low concentration antagonism and high concentration synergy.The dose-response curves show the hormesis effect of low concentration promotion and high concentration inhibition.2)The combined toxicity mechanism of the mixed system of aminoglycoside antibacterial agents-quorum sensing inhibitors andβ-lactam antibacterial agents-quorum sensing inhibitors is that when the mixture concentration is low,aminoglycoside antibacterial agents,β-lactam antibiotics and quorum sensing inhibitors induce Escherichia coli to produce reactive oxygen free radicals and promote the growth of Escherichia coli.Therefore,the combined effect is antagonistic at low concentration;At high concentration,excessive reactive oxygen species causes oxidative damage to Escherichia coli cells,resulting in a large number of Escherichia coli death.3)The 11 tested compounds can promote the mutation of Escherichia coli.The concentrations at the maximum mutation frequency promotion rate are 7.94E-07 mol·L-1（neomycin sulfate）,1.84E-06 mol·L-1（streptomycin sulfate）,5.01E-06 mol·L-1（gentamicin sulfate）,2.51E-06 mol·L-1（amoxicillin trihydrate）,5.01E-06 mol·L-1（cefotaxime sodium）,1.58E-04 mol·L-1（oxacillin sodium）7.94E-03 mol·L-1（2（5H）-furanone）,8.91E-03 mol·L-1（2,5-dimethyl-4-hydroxy-3（2H）-furanone）,7.94E-03 mol·L-1（4-acetoxy-2,5-dimethyl-3-furanone）,3.55E-02 mol·L-1（2-methyltetrahydrofuran-3-one）and 1.12E-02 mol·L-1（3-benzofuranone）;The single mutation effect and combined mutation effect of the tested compound on Escherichia coli,the mutation frequency promotion rate first increased and then decreased with the increase of the concentration of the tested compound,and the dose effect curve showed an inverted"U"shape.4)Aminoglycoside antibacterial agents,β-Lactam antibiotics and quorum sensing inhibitors induce mutations in Escherichia coli by inducing the expression of related genes or the formation of error prone polymerase;Through correlation analysis,it was found that the mechanism of mutation induced by 11 antimicrobial agents was strongly correlated with their toxicity mechanism. |
