Towards a general model for predicting minimal metal concentrations co-selecting for antibiotic resistance plasmids
Towards a general model for predicting minimal metal concentrations co-selecting for antibiotic resistance plasmids
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DOI：
10.1101/2020.09.14.295766
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
Sankalp Arya;Alexander Williams;S. Reina;C. Knapp;Jan-Ulrich Kreft;J. Hobman;D. Stekel
中科院分区：
文献类型：
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作者：
Sankalp Arya;Alexander Williams;S. Reina;C. Knapp;Jan-Ulrich Kreft;J. Hobman;D. Stekel
许多抗生素抗性基因与过渡金属（如铜、锌或汞）的抗性基因共存。在某些环境中，已观察到高金属浓度与抗生素抗性基因的高丰度之间的正相关性，这表明由于金属的存在而导致的共选择。特别值得关注的是铜和锌在畜牧业中的使用，导致动物肠道微生物组、泥浆、粪肥或改良土壤中抗生素耐药性的潜在共同选择。对于抗生素，预测的无作用浓度来自实验室测量的最低抑菌浓度，并在环境设置中研究了一些最低选择性浓度。然而，金属的最小共选择浓度难以确定。在这里，我们使用数学建模提供了一个一般的机制框架，以预测最小的共选择性浓度的金属，在不同浓度的毒性知识。我们将该方法应用于铜（Cu）、锌（Zn）、汞（Hg）、铅（Pb）和银（Ag），预测它们的最小共选择浓度（mg/L）（Cu：5.5，Zn：1.6，Hg：0.0156，Pb：21.5，Ag：0.152）。为了验证这些阈值的使用，我们考虑了来自英国奶牛场的泥浆和泥浆修正土壤的金属浓度，该奶牛场使用铜和锌作为饲料和抗菌足浴的添加剂：预计泥浆是共选择性的，但不是泥浆修正土壤。这一建模框架可用作确定标准的基础，以减轻适用于各种环境的抗菌素耐药性风险，包括粪肥、泥浆和其他废物流。
Many antibiotic resistance genes co-occur with resistance genes for transition metals, such as copper, zinc, or mercury. In some environments, a positive correlation between high metal concentration and high abundance of antibiotic resistance genes has been observed, suggesting co-selection due to metal presence. Of particular concern is the use of copper and zinc in animal husbandry, leading to potential co-selection for antibiotic resistance in animal gut microbiomes, slurry, manure, or amended soils. For antibiotics, predicted no effect concentrations have been derived from laboratory measured minimum inhibitory concentrations and some minimal selective concentrations have been investigated in environmental settings. However, minimal co-selection concentrations for metals are difficult to identify. Here, we use mathematical modelling to provide a general mechanistic framework to predict minimal co-selective concentrations for metals, given knowledge of their toxicity at different concentrations. We apply the method to copper (Cu), Zinc (Zn), mercury (Hg), lead (Pb) and silver (Ag), predicting their minimum co-selective concentrations in mg/L (Cu: 5.5, Zn: 1.6, Hg: 0.0156, Pb: 21.5, Ag: 0.152). To exemplify use of these thresholds, we consider metal concentrations from slurry and slurry-amended soil from a UK dairy farm that uses copper and zinc as additives for feed and antimicrobial footbath: the slurry is predicted to be co-selective, but not the slurry-amended soil. This modelling framework could be used as the basis for defining standards to mitigate risks of antimicrobial resistance applicable to a wide range of environments, including manure, slurry and other waste streams.