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磺胺甲噁唑对质粒介导的抗生素耐药基因水平转移的影响及其作用机制。

Effect of sulfamethazine on the horizontal transfer of plasmid-mediated antibiotic resistance genes and its mechanism of action.

机构信息

National Engineering Laboratory for Efficient Utilization of Soil and Fertilizer Resources, Key Laboratory of Agricultural Environment in Universities of Shandong, College of Resources and Environment, Shandong Agricultural University, Tai'an 271018, China.

Department of Civil and Environmental Engineering, Hanyang University, Seongdong-gu, Seoul 04763, Korea.

出版信息

J Environ Sci (China). 2023 May;127:399-409. doi: 10.1016/j.jes.2022.06.014. Epub 2022 Jun 18.

Abstract

As a new type of environmental pollutant, antibiotic resistance genes (ARGs) pose a huge challenge to global health. Horizontal gene transfer (HGT) represents an important route for the spread of ARGs. The widespread use of sulfamethazine (SM2) as a broad-spectrum bacteriostatic agent leads to high residual levels in the environment, thereby increasing the spread of ARGs. Therefore, we chose to study the effect of SM2 on the HGT of ARGs mediated by plasmid RP4 from Escherichia coli (E. coli) HB101 to E. coli NK5449 as well as its mechanism of action. The results showed that compared with the control group, SM2 at concentrations of 10 mg/L and 200 mg/L promoted the HGT of ARGs, but transfer frequency decreased at concentrations of 100 mg/L and 500 mg/L. The transfer frequency at 200 mg/L was 3.04 × 10, which was 1.34-fold of the control group. The mechanism of SM2 improving conjugation transfer is via enhancement of the mRNA expression of conjugation genes (trbBP, trfAP) and oxidative stress genes, inhibition of the mRNA expression of vertical transfer genes, up regulation of the outer membrane protein genes (ompC, ompA), promotion of the formation of cell pores, and improvement of the permeability of cell membrane to promote the conjugation transfer of plasmid RP4. The results of this study provide theoretical support for studying the spread of ARGs in the environment.

摘要

作为一种新型的环境污染物,抗生素抗性基因(ARGs)对全球健康构成了巨大挑战。水平基因转移(HGT)是 ARGs 传播的重要途径。磺胺二甲嘧啶(SM2)作为一种广谱抑菌剂被广泛使用,导致其在环境中的残留水平很高,从而增加了 ARGs 的传播。因此,我们选择研究 SM2 对大肠杆菌(E. coli)HB101 质粒 RP4 介导的 ARGs 水平基因转移(HGT)的影响及其作用机制。结果表明,与对照组相比,浓度为 10mg/L 和 200mg/L 的 SM2 促进了 ARGs 的 HGT,但在 100mg/L 和 500mg/L 浓度下转移频率降低。200mg/L 时的转移频率为 3.04×10-7,是对照组的 1.34 倍。SM2 提高接合转移的机制是通过增强接合基因(trbBP、trfAP)和氧化应激基因的 mRNA 表达,抑制垂直转移基因的 mRNA 表达,上调外膜蛋白基因(ompC、ompA),促进细胞孔的形成,提高细胞膜的通透性,从而促进质粒 RP4 的接合转移。本研究结果为研究 ARGs 在环境中的传播提供了理论支持。

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