Modelling protection from antimicrobial agents in biofilms through the formation of persister cells
Modelling protection from antimicrobial agents in biofilms through the formation of persister cells
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DOI：
10.1099/mic.0.27385-0
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发表时间：
2005-01-01
期刊：
影响因子：
2.8
通讯作者：
Stewart, PS
中科院分区：
文献类型：
--
作者：
Roberts, ME;Stewart, PS
生物膜动力学的数学模型被用来研究从抗菌剂杀死，可以提供给微生物在生物膜的基础上的机制的“持久”细胞或表型变体形成的保护。持续状态是一种假设的高度保护状态，由生物膜中的一小部分细胞采用。假设以固定速率产生持久性，与底物或抗菌剂的存在无关。假设细胞在暴露于生长基质时从持续状态恢复。认为持效细胞不能生长。该模型预测，持留细胞在生物膜中的数量增加，即使它们不能生长，在底物限制区域积累。在这些区域，正常细胞不能生长，但会慢慢转化为持久状态。在生长培养物中持续存在物形成的计算预测，持续存在物将以低数量存在于生长培养物中，但应在缓慢生长的条件下积累，例如在连续培养物中的非常低的稀释率或在分批培养物中的静止期。当模拟抗生素处理时，生物膜表面附近的细菌被杀死，但生物膜深处的持久性细菌被杀死得很差。在抗生素治疗停止后，存活的持续细胞迅速恢复并允许生物膜重新生长。该建模研究为进一步研究假设的持留细胞状态作为生物膜对抗菌剂耐药性的解释提供了动力。
A mathematical model of biofilm dynamics was used to investigate the protection from antimicrobial killing that could be afforded to micro-organisms in biofilms based on a mechanism of 'persister' cell or phenotypic variant formation. The persister state is a hypothetical, highly protected state adopted by a small fraction of the cells in a biofilm. Persisters were assumed to be generated at a fixed rate, independent of the presence of substrate or antimicrobial agent. Cells were assumed to revert from the persister state when exposed to the growth substrate. Persister cells were assumed to be incapable of growth. The model predicted that persister cells increased in numbers in the biofilm, even though they were unable to grow, accumulating in regions of substrate limitation. In these regions, normal cells failed to grow, but did slowly convert to the persister state. Calculations of persister formation in planktonic cultures predicted that persisters would be present in low numbers in growing cultures, but should accumulate under conditions of slow growth, e.g. very low dilution rates in continuous culture or stationary phase in batch culture. When antibiotic treatment was simulated, bacteria near the biofilm surface were killed, but persisters in the depth of the biofilm were poorly killed. After antibiotic treatment ceased, surviving persister cells quickly reverted and allowed the biofilm to regrow. This modelling study provides motivation for further investigation of the hypothetical persister cell state as an explanation for biofilm resistance to antimicrobial agents.