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首页> 外文期刊>Applied and Environmental Microbiology >Modeling Bacterial Population Growth from Stochastic Single-Cell Dynamics
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Modeling Bacterial Population Growth from Stochastic Single-Cell Dynamics

机译:从随机单细胞动力学模型模拟细菌种群的增长

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A few bacterial cells may be sufficient to produce a food-borne illness outbreak, provided that they are capable of adapting and proliferating on a food matrix. This is why any quantitative health risk assessment policy must incorporate methods to accurately predict the growth of bacterial populations from a small number of pathogens. In this aim, mathematical models have become a powerful tool. Unfortunately, at low cell concentrations, standard deterministic models fail to predict the fate of the population, essentially because the heterogeneity between individuals becomes relevant. In this work, a stochastic differential equation (SDE) model is proposed to describe variability within single-cell growth and division and to simulate population growth from a given initial number of individuals. We provide evidence of the model ability to explain the observed distributions of times to division, including the lag time produced by the adaptation to the environment, by comparing model predictions with experiments from the literature for Escherichia coli, Listeria innocua, and Salmonella enterica. The model is shown to accurately predict experimental growth population dynamics for both small and large microbial populations. The use of stochastic models for the estimation of parameters to successfully fit experimental data is a particularly challenging problem. For instance, if Monte Carlo methods are employed to model the required distributions of times to division, the parameter estimation problem can become numerically intractable. We overcame this limitation by converting the stochastic description to a partial differential equation (backward Kolmogorov) instead, which relates to the distribution of division times. Contrary to previous stochastic formulations based on random parameters, the present model is capable of explaining the variability observed in populations that result from the growth of a small number of initial cells as well as the lack of it compared to populations initiated by a larger number of individuals, where the random effects become negligible.
机译:少数细菌细胞可能足以引起食源性疾病爆发,只要它们能够在食物基质上适应和增殖即可。这就是为什么任何定量的健康风险评估政策都必须采用能够准确预测少数病原体细菌种群增长的方法的原因。为此,数学模型已成为强大的工具。不幸的是,在低细胞浓度下,标准的确定性模型无法预测种群的命运,这主要是因为个体之间的异质性变得很重要。在这项工作中,提出了一种随机微分方程(SDE)模型来描述单细胞生长和分裂的变异性,并模拟给定初始数量的个体的种群增长。通过将模型预测与大肠杆菌,李斯特菌和肠炎沙门氏菌文献中的实验进行比较,我们提供了模型能力来解释观察到的分裂时间分布的证据,包括适应环境产生的滞后时间。该模型显示可以准确预测小型和大型微生物种群的实验生长种群动态。使用随机模型来估计参数以成功拟合实验数据是一个特别具有挑战性的问题。例如,如果采用蒙特卡洛方法对除法所需的时间分布进行建模,则参数估计问题可能在数值上变得棘手。我们通过将随机描述转换为偏微分方程(向后Kolmogorov)来克服此限制,该偏微分方程与除法时间的分布有关。与以前基于随机参数的随机公式相反,本模型能够解释由于少量初始细胞的生长以及与大量初始细胞的缺乏相比导致的种群中的变异性。个人,其随机影响可以忽略不计。

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