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Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration.
Communications Biology ( IF 5.9 ) Pub Date : 2020-09-03 , DOI: 10.1038/s42003-020-01176-w
Isobel C Stanton 1 , Aimee K Murray 1 , Lihong Zhang 1 , Jason Snape 2 , William H Gaze 1
Affiliation  

Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commissionʼs Water Framework Directive’s priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1–2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.



中文翻译:

低抗生素浓度下抗生素耐药性的演变,包括低于最低选择浓度的选择。

确定抗生素在环境浓度下的选择性潜力对于设计有效策略以限制抗生素耐药性的选择至关重要。本研究确定了欧盟委员会水框架指令的优先危险物质观察清单中包含的大环内酯类和氟喹诺酮类抗生素的最低选择性浓度 (MSC)。大环内酯类在比测量的环境浓度 ( MEC) 高1-2 个数量级 (>500 和 <750 µg/L) 时显示出对ermF 的阳性选择。环丙沙星说明了对intI1 的阳性选择浓度类似于当前的 MEC(>7.8 和 <15.6 µg/L)。这突出了对选择性潜力进行化合物特异性评估的必要性。此外,还描述了由最小增加的持久性浓度 (MIPC) 定义的亚 MSC 选择性窗口。相对于 MSC 以下的无抗生素对照,阴性选择(或持续性)的差异率与患病率升高有关。这种增加的持久性导致随着时间的推移进行进一步选择的机会以及人类接触和环境传播的风险。

更新日期:2020-09-03
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