Institute of Hydrobiology, TU Dresden, Zellescher Weg 40, Dresden 01217, Germany.
Institute of Hydrobiology, TU Dresden, Zellescher Weg 40, Dresden 01217, Germany.
Sci Total Environ. 2021 Dec 1;798:149174. doi: 10.1016/j.scitotenv.2021.149174. Epub 2021 Jul 22.
The accelerated spread of antibiotic resistance genes (ARG) in the environment occurs mainly through plasmid transfer facilitated via bacterial conjugation. To predict and efficiently counteract the problems associated with ARG transmission, it is important to estimate conjugation rates under different experimental conditions. The classical models typically used to estimate parameters for mating experiments, while pragmatic in calculating growth and plasmid transfer, often ignore processes such as the reduction in growth due to plasmid bearing costs and are non-inclusive of environmental influences like temperature effects. Here, we present a process-based numerical model taking into account the fitness cost associated with plasmid carriage and temperature dependencies in vertical and horizontal gene transfer processes. Observations from liquid culture conjugation experiments using Escherichia coli and the plasmid pB10 were used to validate our proposed model. We present a comparison between the parameters estimated using the existing and the proposed model. Uncertainties in the estimated parameters were quantified using classical and advanced Bayesian methods. For our mating experiments, we found that at temperatures between 20 and 37 °C, the plasmid bearing costs reduced the growth rates by > 35%. The temperature dependency model of conjugation showed a good fit (mean absolute percentage error < 10%) independent of the bacteria and the plasmid under study. The proposed model simultaneously estimates growth and plasmid transfer rate constants for all three strains (donor, recipient, and transconjugant). Simultaneous estimation of growth and conjugation parameters is particularly useful to estimate the spread of ARG when one of the mating partners inhibits the growth of the other, which is common in multi-species mating or when the incurred plasmid costs are situation dependent (e.g., increased plasmid cost in a mating environment) as observed in this study.
抗生素耐药基因 (ARG) 在环境中的快速传播主要通过细菌接合介导的质粒转移来实现。为了预测和有效地应对与 ARG 传播相关的问题，重要的是要估计不同实验条件下的接合率。经典模型通常用于估计交配实验的参数，虽然在计算生长和质粒转移方面很实用，但往往忽略了由于携带质粒而导致生长减少的过程，并且不包括温度等环境影响。在这里，我们提出了一个基于过程的数值模型，该模型考虑了与质粒携带相关的适应成本以及垂直和水平基因转移过程中的温度依赖性。使用大肠杆菌和质粒 pB10 进行的液体培养交配实验的观察结果用于验证我们提出的模型。我们比较了使用现有模型和提出的模型估计的参数。使用经典和先进的贝叶斯方法量化了估计参数的不确定性。对于我们的交配实验，我们发现在 20 到 37°C 之间的温度下，携带质粒的成本降低了超过 35%的生长速率。 conjugation 的温度依赖性模型具有良好的拟合度（平均绝对百分比误差 <10%），独立于所研究的细菌和质粒。所提出的模型同时估计了所有三个菌株（供体、受体和转导子）的生长和质粒转移率常数。同时估计生长和接合参数对于估计 ARG 的传播特别有用，当其中一个交配伙伴抑制另一个生长时，这在多物种交配中很常见，或者当所产生的质粒成本取决于情况时（例如，在交配环境中增加质粒成本），正如本研究中观察到的那样。
