银系抗菌剂与有机抗菌剂对大肠杆菌的联合毒性效应  

A study on the combined toxicities of silver antibacterial agents and organic antibacterial agents against Escherichia coli

作　　者：包诗玉 孙昊宇[2] 龙茜[2] 张跃恒 林志芬[2] 印春生 BAO Shiyu;SUN Haoyu;LONG Xi;ZHANG Yueheng;LIN Zhifen;YIN Chunsheng(College of Marine Science,Shanghai Ocean University,Shanghai,201306,China;State Key Laboratory of Pollution Control and Resource Reuse,College of Environmental Science and Engineering,Tongji University,Shanghai,200092,China)

机构地区：[1]上海海洋大学海洋生态与环境学院,上海201306 [2]污染控制与资源化研究国家重点实验室,同济大学环境科学与工程学院,上海200092

出　　处：《环境化学》2022年第3期871-882,共12页Environmental Chemistry

基　　金：国家自然科学基金(22006116,21777123);同济大学污染控制与资源化研究国家重点实验室自主研究(重点)项目(PCRRK16007);博士后创新人才支持计划(BX20190247);中国博士后科学基金(2019M661624);上海“超级博士后”激励计划(2019194)资助

摘　　要：抗菌剂的长期滥用导致细菌耐药性问题不断加剧,这对人类的健康生存和长期发展构成巨大威胁。银系抗菌剂作为不易产生耐药性的无机抗菌材料,可以将其与有机抗菌剂联合使用以提高抗菌效果,从而达到减少抗菌剂滥用的目的。但由于有机抗菌剂的结构及单一作用机制不同,使得银系抗菌剂与其联合后会产生不同的抗菌效果,因此有必要研究银系抗菌剂与不同的有机抗菌剂的联合毒性效应。本文以大肠杆菌为模式生物,硝酸银(AgNO_(3))和纳米银(AgNPs)作为常见的银类抗菌剂,测定了AgNO_(3)、AgNPs与8种有机抗菌剂(多肽类、表面活性剂类、糖肽类、β-内酰胺类、唑啉类、氨基糖苷类、四环素类和大环内酯类)在1∶1、1∶5和5∶1毒性比混合下的联合毒性。结果表明,AgNO_(3)和AgNPs在单一毒性实验和混合毒性中主要通过释放Ag+来发挥其对大肠杆菌的毒性作用。此外,8种有机抗菌剂中仅有氨基糖苷类抗生素与银系抗菌剂在所有毒性比的联合作用下均呈现协同效应。为了进一步验证这一协同作用的普遍性,测定了AgNO_(3)和AgNPs与另外5种氨基糖苷类抗生素在1∶1、1∶5和5∶1毒性比联合的毒性效应。结果显示AgNO_(3)和AgNPs与大部分氨基糖苷类抗生素的联合毒性作用呈现协同效应。基于银系抗菌剂与氨基糖苷类抗生素的毒性作用机理,推测这两者的协同抗菌效应可能是由于银系抗菌剂作用的蛋白酶与氨基糖苷类抗生素作用的核糖体具有通路一致性,它们联合作用协同破坏了蛋白质合成与代谢的整个过程。本研究可以为今后抗菌剂的联合用药和探索更多的抗菌剂联合协同治疗方案提供参考和新思路,并为多种抗菌剂在环境中联合暴露的风险评价提供参考。The abuse of antibiotics has caused increasingly serious bacterial resistance,which poses a great threat to human health and long-term development.Silver antimicrobial is a kind of inorganic antibacterial material and is not easy to induce drug resistance,which is suggested to be used together with organic antibacterial agents to improve the antibacterial effect and reduce the use of antibiotics.However,due to the different structures and single action mechanisms of organic antibacterial agents,their combined use with silver antimicrobials may trigger different antibacterial effects.Therefore,it is necessary to explore the combined toxic effects between silver antimicrobials and different organic antibacterial agents.In this paper,Escherichia coli(E.coli)was used as the model organism,while silver nitrate(AgNO_(3))and nano silver(AgNPs)were chosen as the test silver antimicrobials.The combined toxicity of 2 silver antimicrobials(AgNO_(3),and AgNPs)and 8 organic antibacterial agents(Polypeptide,Surfactant,β-lactam,Glycopeptide,Azoline fungicide,Tetracycline,Macrolide,Aminoglycoside)were determined as the toxicity ratios setting at 1∶1,1∶5 and 5∶1.The results indicated that the toxic effects of AgNO_(3) and AgNPs in single and combined toxicity are mainly derived from the release of Ag+.Among the 8 organic antibacterial agents,only aminoglycoside exhibited synergistic effect with silver antimicrobials at all toxicity ratios.To further verify the universality of this synergism,the combined toxicity of silver antimicrobials and five other aminoglycosides were tested as the toxicity ratios setting at 1∶1,1∶5 and 5∶1,which all showed the synergism in these mixtures.Based on the toxic mechanisms of silver antimicrobials and aminoglycoside,it was speculated that the synergistic effects of silver antimicrobials and aminoglycosides might result from that the target of silver antimicrobials(protease)and the target of aminoglycoside(ribosome)lie in the same signaling pathway,and thus their combined use synergist

关 键 词：银系抗菌剂 有机抗菌剂 氨基糖苷类抗生素 大肠杆菌 联合毒性作用 协同机制 

分 类 号：X171.5[环境科学与工程—环境科学]