Spatio-temporal modeling of the crowding conditions and metabolic variability in microbial communities.
Spatio-temporal modeling of the crowding conditions and metabolic variability in microbial communities.
复制标题
DOI：
10.1371/journal.pcbi.1009140
复制
发表时间：
2021-07
影响因子：
4.3
通讯作者：
Hatzimanikatis V
中科院分区：
文献类型：
--
作者：
Angeles-Martinez L;Hatzimanikatis V
物种的代谢能力和当地环境通过代谢产物的交换或对资源的竞争来塑造群落中的微生物相互作用。细胞通常排列得非常接近，形成了一个拥挤的环境，不均匀地减少了营养物质的扩散。在此，我们研究了细胞之间的拥挤条件和代谢变异性如何塑造微生物群落的动态。为此，我们开发了CROMICS，这是一个时空框架，它结合了基于个体的建模，缩放粒子理论和热力学通量分析等技术，以明确地将细胞代谢和大分子组分的存在对营养物质扩散的影响结合起来。该框架用于研究两种典型的微生物群落（i）通过交换代谢物相互合作的大肠杆菌和肠道沙门氏菌，以及（ii）两种大肠杆菌。大肠杆菌的胞外聚合物（EPS）的产生水平不同，竞争相同的营养物质。在互惠共生社区中，我们的研究结果表明，拥挤通过减少代谢产物从产生它们的区域的泄漏，避免与非合作细胞的资源竞争来增强合作突变体的适应性。此外，我们还证明了E.大肠杆菌分泌EPS的突变体通过产生较低密度的结构（即增加细胞之间的间距）赢得了与非分泌细胞的竞争，该结构允许突变体扩展并到达更靠近营养供应点的区域。当考虑到拥挤效应时，EPS分泌细胞相对于非分泌细胞的相对适合度有适度的提高。细胞间相互作用的出现和细胞内的冲突所产生的生长和代谢产物或EPS的分泌之间的权衡可以提供一个物种的本地竞争优势，无论是通过提供更多的交叉喂养代谢物或通过创建一个不太密集的邻居。微生物群落在生物地球化学循环、生物修复和人类健康中起着关键作用。在拥挤的微生物系统如生物膜和细胞聚集体中，单个细胞之间的紧密接近减少了营养物质扩散的自由空间。为了模拟这些微生物系统的异质性，我们开发了CROMICS，这是一个框架，它整合了每个细胞的代谢能力以及培养基中细胞和大分子的大小和位置的信息。个体之间的相互作用通过竞争或交换代谢物而自然产生。我们展示了在拥挤的环境中突变体的存在和扩散的减少如何扰乱当地营养物质的可用性，从而改变微生物群落的动态。在拥挤的系统中发现的微生物相互作用的机制以及开发的框架代表了未来研究人类微生物组和宿主代谢，病原体入侵和抗生素有效性评估的相互作用的有价值的起点。
The metabolic capabilities of the species and the local environment shape the microbial interactions in a community either through the exchange of metabolic products or the competition for the resources. Cells are often arranged in close proximity to each other, creating a crowded environment that unevenly reduce the diffusion of nutrients. Herein, we investigated how the crowding conditions and metabolic variability among cells shape the dynamics of microbial communities. For this, we developed CROMICS, a spatio-temporal framework that combines techniques such as individual-based modeling, scaled particle theory, and thermodynamic flux analysis to explicitly incorporate the cell metabolism and the impact of the presence of macromolecular components on the nutrients diffusion. This framework was used to study two archetypical microbial communities (i) Escherichia coli and Salmonella enterica that cooperate with each other by exchanging metabolites, and (ii) two E. coli with different production level of extracellular polymeric substances (EPS) that compete for the same nutrients. In the mutualistic community, our results demonstrate that crowding enhanced the fitness of cooperative mutants by reducing the leakage of metabolites from the region where they are produced, avoiding the resource competition with non-cooperative cells. Moreover, we also show that E. coli EPS-secreting mutants won the competition against the non-secreting cells by creating less dense structures (i.e. increasing the spacing among the cells) that allow mutants to expand and reach regions closer to the nutrient supply point. A modest enhancement of the relative fitness of EPS-secreting cells over the non-secreting ones were found when the crowding effect was taken into account in the simulations. The emergence of cell-cell interactions and the intracellular conflicts arising from the trade-off between growth and the secretion of metabolites or EPS could provide a local competitive advantage to one species, either by supplying more cross-feeding metabolites or by creating a less dense neighborhood. Microbial communities play a key role in biogeochemical cycles, bioremediation, and human health. In crowded microbial systems such as biofilms and cellular aggregates, the close proximity between individual cells reduces the free space for the nutrients diffusion. To model the heterogeneous nature of these microbial systems, we developed CROMICS, a framework that integrates the information about the metabolic capabilities of each individual cell as well as the size and location of cells and macromolecules in the medium. The interactions among the individuals arise naturally through competition for or the exchange of metabolites. We show how the presence of mutants and a reduced diffusion in crowded environments can perturb the local availability of nutrients and therefore modify the dynamics of a microbial community. The discovered mechanisms underlying the microbial interactions in crowded systems together with the developed framework represent a valuable starting point for future studies of the interplay of human microbiome and host metabolism, the pathogen invasion, and the evaluation of antibiotic effectiveness.
登录
查看更多内容
影响因子：
16.8
作者：
Dal Co, Alma;van Vliet, Simon;Ackermann, Martin
通讯作者：
Ackermann, Martin
影响因子：
2.2
作者：
Jain, AK;Mao, JC;Mohiuddin, KM
通讯作者：
Mohiuddin, KM
影响因子：
7.7
作者：
Momeni B;Waite AJ;Shou W
通讯作者：
Shou W
影响因子：
4.4
作者：
LEBOWITZ, JL;HELFAND, E;PRAESTGAARD, E
通讯作者：
PRAESTGAARD, E
影响因子：
3.4
作者：
Angeles-Martinez, Liliana;Theodoropoulos, Constantinos
通讯作者：
Theodoropoulos, Constantinos