Horizontal gene transfer is an essential component of bacterial evolution. Quantitative information on transfer rates is particularly useful to better understand and possibly predict the spread of antimicrobial resistance. A variety of methods has been proposed to estimate the rates of plasmid-mediated gene transfer all of which require substantial labor input or financial resources. A cheap but reliable method with high-throughput capabilities is yet to be developed in order to better capture the variability of plasmid transfer rates, e.g. among strains or in response to environmental cues. We explored a new approach to the culture-based estimation of plasmid transfer rates in liquid media allowing for a large number of parallel experiments. It deviates from established approaches in the fact that it exploits data on the absence/presence of transconjugant cells in the wells of a well plate observed over time. Specifically, the binary observations are compared to the probability of transconjugant detection as predicted by a dynamic model. The bulk transfer rate is found as the best-fit value of a designated model parameter. The feasibility of the approach is demonstrated on mating experiments where the RP4 plasmid is transfered from Serratia marcescens to several Escherichia coli recipients. The method's uncertainty is explored via split sampling and virtual experiments.

中文翻译：

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一种高通量方法，用于基于培养物的质粒转移速率估计。

水平基因转移是细菌进化的重要组成部分。关于转移速率的定量信息对于更好地了解并可能预测抗菌素耐药性的传播特别有用。已经提出了多种方法来估计质粒介导的基因转移的速率，所有这些都需要大量的劳动投入或财力。为了更好地捕获质粒转移速率的可变性，例如在菌株之间或响应环境提示，尚未开发出具有高通量能力的廉价但可靠的方法。我们探索了一种新的方法，用于基于培养基的液体培养基中质粒转移速率的估计，可进行大量平行实验。它偏离了已建立的方法，因为它利用了随时间推移观察到的孔板孔中是否存在转导结合细胞的数据。具体而言，将二元观测值与动态模型预测的跨共轭检测的可能性进行比较。找到批量传输率作为指定模型参数的最佳拟合值。在将RP4质粒从粘质沙雷氏菌转移到数个大肠杆菌受体的交配实验中证明了该方法的可行性。通过拆分采样和虚拟实验来探索该方法的不确定性。找到批量传输率作为指定模型参数的最佳拟合值。在将RP4质粒从粘质沙雷氏菌转移到数个大肠杆菌受体的交配实验中证明了该方法的可行性。通过拆分采样和虚拟实验来探索该方法的不确定性。找到批量传输率作为指定模型参数的最佳拟合值。在将RP4质粒从粘质沙雷氏菌转移到几个大肠杆菌受体的交配实验中证明了该方法的可行性。通过拆分采样和虚拟实验来探索该方法的不确定性。