BacSim, a simulator for individual-based modelling of bacterial colony growth
BacSim, a simulator for individual-based modelling of bacterial colony growth
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DOI：
10.1099/00221287-144-12-3275
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发表时间：
1998-12-01
期刊：
影响因子：
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通讯作者：
Wimpenny, JWT
中科院分区：
文献类型：
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作者：
Kreft, JU;Booth, G;Wimpenny, JWT
开发了通用的、定量的、空间明确的、基于个体的模型BacSim来模拟细菌的生长和行为。这种方法的潜力在于将微观实体（细胞）的性质与宏观复杂系统（如生物膜）的性质联系起来。在这里，研究了单个大肠杆菌细胞生长成菌落。面向对象的程序BacSim是Gecko的扩展，Gecko是一个生态系统动力学模型，它使用Swarm工具包进行多代理模拟。该模型描述了细菌的特性，包括底物摄取，代谢，维持，细胞分裂和死亡在单个细胞水平。为了使该模型易于适用于不同条件下的各种细菌，该模型使用了少至8个容易获得的参数，这些参数可以随机变化。对于衬底扩散，使用二维扩散晶格。对于生长速率依赖的细胞大小的变化，由Donachie提出的细胞分裂的概念模型进行了检查。多纳奇模型的一个机械版本导致了在更高的增长率下的不平衡增长，而在随后的复制启动之间包括一个最小的时间段，只有当这个时间段长得不符合生理学时，才能确保平衡增长。只有描述性版本的Donachie模型预测细胞大小正确。对于维持，实施赫伯特模型（生物质消耗的恒定比速率），对于底物吸收，实施Michaelis-Menten或Best方程。模拟器输出忠实地再现了所有输入参数。生长特性时，维持和摄取率成比例的细胞质量或表面积进行了比较。作者提出了一种新的通用测量生长同步性，以量化由于细胞参数的随机变化或空间异质性而导致的同步性丧失。最大摄取速率的变化完全使模拟培养物去极化，但分裂体积的变化不会。引入了一种新的空间异质性度量：细胞所经历的底物浓度的标准差。空间异质性通过将种群细分为以不同速率同步增长的部分来降低种群增长。在足够高的空间异质性，人口似乎完全异步增长。
The generic, quantitative, spatially explicit, individual-based model BacSim was developed to simulate growth and behaviour of bacteria. The potential of this approach is in relating the properties of microscopic entities - cells - to the properties of macroscopic, complex systems such as biofilms. Here, the growth of a single Escherichia coli cell into a colony was studied. The object-oriented program BacSim is an extension of Gecko, an ecosystem dynamics model which uses the Swarm toolkit for multi-agent simulations. The model describes bacterial properties including substrate uptake, metabolism, maintenance, cell division and death at the individual cell level. With the aim of making the model easily applicable to various bacteria under different conditions, the model uses as few as eight readily obtainable parameters which can be randomly varied. For substrate diffusion, a two-dimensional diffusion lattice is used. For growth-rate-dependent cell size variation, a conceptual model of cell division proposed by Donachie was examined. A mechanistic version of the Donachie model led to unbalanced growth at higher growth rates, whereas including a minimum period between subsequent replication initiations ensured balanced growth only if this period was unphysiologically long. Only a descriptive version of the Donachie model predicted cell sizes correctly. For maintenance, the Herbert model (constant specific rate of biomass consumption) and for substrate uptake, the Michaelis-Menten or the Best equations were implemented. The simulator output faithfully reproduced all input parameters. Growth characteristics when maintenance and uptake rates were proportional to either cell mass or surface area are compared. The authors propose a new generic measure of growth synchrony to quantify the loss of synchrony due to random variation of cell parameters or spatial heterogeneity. Variation of the maximal uptake rate completely desynchronizes the simulated culture but variation of the volume-at-division does not. A new measure for spatial heterogeneity is introduced: the standard deviation of substrate concentrations as experienced by the cells. Spatial heterogeneity desynchronizes population growth by subdividing the population into parts synchronously growing at different rates. At a high enough spatial heterogeneity, the population appears to grow completely asynchronously.