Emergence and selection of antibiotic resistance following exposure to high antibiotic concentrations have been repeatedly shown in clinical and agricultural settings, whereas the role of the weak selective pressures exerted by antibiotic levels below the MIC (sub-MIC) in aquatic environments due to anthropogenic contamination remains unclear. Here, we studied how exposure to sub-MIC levels of ciprofloxacin enriches for Escherichia coli with reduced susceptibility to ciprofloxacin using a mallard colonization model. Mallards were inoculated with two isogenic extended-spectrum-β-lactamase (ESBL)-encoding E. coli strains, differing only by a gyrA mutation that results in increased MICs of ciprofloxacin, and exposed to different levels of ciprofloxacin in their swimming water. Changes in the ratios of mutant to parental strains excreted in feces over time and ESBL plasmid spread within the gut microbiota from individual birds were investigated. Results show that in vivo selection of gyrA mutants occurred in mallards during exposure to ciprofloxacin at concentrations previously found in aquatic environments. During colonization, resistance plasmids were readily transferred between strains in the intestines of the mallards, but conjugation frequencies were not affected by ciprofloxacin exposure. Our results highlight the potential for enrichment of resistant bacteria in wildlife and underline the importance of reducing antibiotic pollution in the environment.

中文翻译：

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水环境中环丙沙星亚抑制浓度暴露的野鸭抗性细菌的选择

在临床和农业环境中反复显示暴露于高浓度抗生素后抗生素耐药性的出现和选择，而由于人为污染，抗生素水平低于 MIC（亚 MIC）在水生环境中所施加的弱选择压力的作用仍然存在不清楚。在这里，我们使用野鸭定植模型研究了暴露于亚 MIC 水平的环丙沙星如何富集大肠杆菌并降低对环丙沙星的敏感性。野鸭接种了两种同基因超广谱-β-内酰胺酶 (ESBL) 编码的大肠杆菌菌株，仅通过gyrA不同导致环丙沙星 MIC 增加的突变，并在游泳水中暴露于不同水平的环丙沙星。研究了随时间推移在粪便中排泄的突变株与亲本菌株的比率的变化以及 ESBL 质粒在个体鸟类肠道微生物群中的传播。结果表明gyrA的体内选择在暴露于先前在水生环境中发现的浓度的环丙沙星期间，野鸭中出现了突变体。在定植期间，抗性质粒很容易在野鸭肠道的菌株之间转移，但结合频率不受环丙沙星暴露的影响。我们的结果强调了在野生动物中富集耐药细菌的潜力，并强调了减少环境中抗生素污染的重要性。