Liang Hebin, Zhang Jiayu, Hu Jiahui, Li Xiaoyan, Li Bing
State Environmental Protection Key Laboratory of Microorganism Application and Risk Control,Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental Safety, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Environ Sci Technol. 2023 Mar 28;57(12):4784-4795. doi: 10.1021/acs.est.2c04999. Epub 2023 Mar 14.
Extensive antibiotic use increases the environmental presence of their residues and may accelerate the development of antibiotic resistance, although this remains poorly understood at environmentally relevant concentrations. Herein, susceptible K12 was continuously exposed to five antibiotics at such concentrations for 100 days. The -evolved mutants rapidly obtained fluoroquinolone resistance within 10 days, as indicated by the 4- and 16-fold augmentation of minimum inhibitory concentrations against enrofloxacin and ciprofloxacin, respectively. Moreover, the mutants maintained heritable fluoroquinolone resistance after the withdrawal of antibiotics for 30 days. Genomic analysis identified Asp87Gly or Ser83Leu substitutions in the A gene in the mutants. Transcriptomics data showed that the transcriptional response of the mutants to fluoroquinolones was primarily involved in biofilm formation, cellular motility, porin, oxidative stress defense, and energy metabolism. Homologous recombination and molecular docking revealed that mutations of A primarily mainly conferred fluoroquinolone resistance, while mutations at different positions of A likely endowed different fluoroquinolone resistance levels. Collectively, this study revealed that environmentally relevant concentrations of antibiotics could rapidly induce heritable antibiotic resistance; therefore, the discharge of antibiotics into the environment should be rigorously controlled to prevent the development of antibiotic resistance.
广泛使用抗生素会增加其残留物在环境中的存在，并可能加速抗生素耐药性的发展，尽管在与环境相关的浓度下，这一点仍知之甚少。在此，敏感的K12在这样的浓度下连续暴露于五种抗生素100天。如对恩诺沙星和环丙沙星的最低抑菌浓度分别增加4倍和16倍所示，进化后的突变体在10天内迅速获得了氟喹诺酮耐药性。此外，在停用抗生素30天后，这些突变体仍保持可遗传的氟喹诺酮耐药性。基因组分析确定了突变体A基因中的Asp87Gly或Ser83Leu替代。转录组学数据表明，突变体对氟喹诺酮的转录反应主要涉及生物膜形成、细胞运动性、孔蛋白、氧化应激防御和能量代谢。同源重组和分子对接表明，A基因的突变主要赋予氟喹诺酮耐药性，而A基因不同位置的突变可能赋予不同水平的氟喹诺酮耐药性。总的来说，这项研究表明，与环境相关浓度的抗生素可以迅速诱导可遗传的抗生素耐药性；因此，应严格控制抗生素向环境中的排放，以防止抗生素耐药性的发展。
