Department of Aquaculture, College of Animal Science and Technology, Northwest A&F University, Xinong Road 22, Yangling, Shaanxi, 712100, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
Environ Pollut. 2023 Jun 1;326:121457. doi: 10.1016/j.envpol.2023.121457. Epub 2023 Mar 21.
Overuse of antimicrobial agents are generally considered to be a key factor in the occurrence of antibiotic resistance bacteria (ARB). Nevertheless, it is unclear whether ARB can be induced by non-antibiotic chemicals such as nonsteroidal anti-inflammatory drug (NSAID). Thus, the objective of this study is to investigate whether NSAID diclofenac (DCF) promote the emergence of antibiotic resistance in Escherichia coli K12 MG1655. Our results suggested that DCF induced the occurrence of ARB which showed hereditary stability of resistance. Meanwhile, gene variation was identified on chromosome of the ARB, and DCF can cause bacterial oxidative stress and SOS response. Subsequently, transcriptional levels of antioxidant (soxS, sodA, sodC, gor, katG, ahpF) and SOS (recA, lexA, uvrA, uvrB, ruvA, ruvB, dinB, umuC, polB) system-related genes were enhanced. However, the expression of related genes cannot be increased in high-dosage treatment compared with low-dosage samples because of cytotoxicity and cellular damage. Simultaneously, high-dosage DCF decreased the mutation frequency but enhanced the resistance of mutants. Our findings expand our knowledge of the promoting effect on the emergence of ARB caused by DCF. More attention and regulations should be given to these potential ecological and health risks for widespread DCF.
过度使用抗菌剂通常被认为是抗生素耐药菌（ARB）发生的一个关键因素。然而，ARB 是否可以被非抗生素化学物质如非甾体抗炎药（NSAID）诱导尚不清楚。因此，本研究的目的是调查 NSAID 双氯芬酸（DCF）是否会促进大肠杆菌 K12 MG1655 产生抗生素耐药性。我们的结果表明，DCF 诱导了 ARB 的发生，其表现出遗传稳定性的耐药性。同时，在 ARB 的染色体上发现了基因变异，并且 DCF 可以引起细菌氧化应激和 SOS 反应。随后，抗氧化（soxS、sodA、sodC、gor、katG、ahpF）和 SOS（recA、lexA、uvrA、uvrB、ruvA、ruvB、dinB、umuC、polB）系统相关基因的转录水平增强。然而，由于细胞毒性和细胞损伤，高剂量处理与低剂量样品相比，相关基因的表达不能增加。同时，高剂量 DCF 降低了突变频率，但增强了突变体的耐药性。我们的发现扩展了我们对 DCF 引起 ARB 发生的促进作用的认识。应该更加关注和规范这些广泛存在的 DCF 所带来的潜在生态和健康风险。
