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生物膜发育过程中细胞死亡的动态建模。

Dynamic modelling of cell death during biofilm development.

机构信息

Systems Biology, School of Life Sciences, University of Skövde, Skövde, Sweden.

出版信息

J Theor Biol. 2012 Feb 21;295:23-36. doi: 10.1016/j.jtbi.2011.10.007. Epub 2011 Nov 11.

DOI:10.1016/j.jtbi.2011.10.007
PMID:22100489
Abstract

Biofilms are currently recognised as the predominant bacterial life-style and it has been suggested that biofilm development is influenced by a number of different processes such as adhesion, detachment, mass transport, quorum sensing, cell death and active dispersal. One of the least understood processes and its effects on biofilm development is cell death. However, experimental studies suggest that bacterial death is an important process during biofilm development and many studies show a relationship between cell death and dispersal in microbial biofilms. We present a model of the process of cell death during biofilm development, with a particular focus on the spatial localisation of cell death or cell damage. Three rules governing cell death or cell damage were evaluated which compared the effects of starvation, damage accumulation, and viability during biofilm development and were also used to design laboratory based experiments to test the model. Results from model simulations show that actively growing biofilms develop steep nutrient gradients within the interior of the biofilm that affect neighbouring microcolonies resulting in cell death and detachment. Two of the rules indicated that high substrate concentrations lead to accelerated cell death, in contrast to the third rule, based on the accumulation of damage, which predicted earlier cell death for biofilms grown with low substrate concentrations. Comparison of the modelling results with experimental results suggests that cell death is favoured under low nutrient conditions and that the accumulation of damage may be the main cause of cell death during biofilm development.

摘要

生物膜目前被认为是细菌的主要生存方式,据认为生物膜的形成受到许多不同过程的影响,如黏附、脱落、物质传输、群体感应、细胞死亡和主动分散。其中,细胞死亡是一个了解最少的过程及其对生物膜形成的影响。然而,实验研究表明,细菌死亡是生物膜形成过程中的一个重要过程,许多研究表明微生物生物膜中细胞死亡和分散之间存在关系。我们提出了一个生物膜形成过程中细胞死亡的模型,特别关注细胞死亡或细胞损伤的空间定位。评估了三个控制细胞死亡或细胞损伤的规则,这些规则比较了饥饿、损伤积累和生物膜形成过程中的生存能力的影响,同时还用于设计实验室实验来测试该模型。模型模拟的结果表明,活跃生长的生物膜在生物膜内部形成陡峭的营养梯度,影响邻近的微菌落,导致细胞死亡和脱落。其中两个规则表明,高底物浓度会加速细胞死亡,而第三个规则则基于损伤的积累,预测在低底物浓度下生长的生物膜会更早发生细胞死亡。将模型模拟结果与实验结果进行比较表明,细胞死亡在低营养条件下更为有利,而损伤的积累可能是生物膜形成过程中细胞死亡的主要原因。

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