环境中的氟喹诺酮类残留物可快速诱导大肠杆菌的遗传性氟喹诺酮类耐药性,Environmental Science & Technology

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环境中的氟喹诺酮类残留物可快速诱导大肠杆菌的遗传性氟喹诺酮类耐药性
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-03-14 , DOI: 10.1021/acs.est.2c04999
Hebin Liang _{1,

2,

3} , Jiayu Zhang _{1,

2,

3} , Jiahui Hu ₄ , Xiaoyan Li _{1,

2,

3} , Bing Li _{1,

2,

3}

Affiliation

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，尽管这在环境相关浓度下仍然知之甚少。在此，易感大肠杆菌K12 连续暴露于这种浓度的五种抗生素 100 天。从头进化的突变体在 10 天内迅速获得氟喹诺酮类耐药性，如对恩诺沙星和环丙沙星的最小抑制浓度分别增加 4 倍和 16 倍所表明的。此外，突变体在停用抗生素 30 天后仍保持可遗传的氟喹诺酮类耐药性。基因组分析确定了gyr中的 Asp87Gly 或 Ser83Leu 替换突变体中的一个基因。转录组学数据表明，突变体对氟喹诺酮类药物的转录反应主要涉及生物膜形成、细胞运动、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，gyr A的突变主要导致氟喹诺酮耐药，而gyr A不同位置的突变可能赋予不同的氟喹诺酮耐药水平。总的来说，这项研究表明，与环境相关的抗生素浓度可以迅速诱发可遗传的抗生素耐药性；因此，应严格控制抗生素排放到环境中，以防止抗生素耐药性的发展。

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Fluoroquinolone Residues in the Environment Rapidly Induce Heritable Fluoroquinolone Resistance in Escherichia coli

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 Escherichia coli K12 was continuously exposed to five antibiotics at such concentrations for 100 days. The de novo-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 gyrA 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 gyrA primarily mainly conferred fluoroquinolone resistance, while mutations at different positions of gyrA 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.

更新日期：2023-03-14

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