Heterogenous Biofilm Mass-Transport Model Replicates Periphery Sequestration of Antibiotics in P. aeruginosa PAO1 Microcolonies.
Heterogenous Biofilm Mass-Transport Model Replicates Periphery Sequestration of Antibiotics in P. aeruginosa PAO1 Microcolonies.
复制标题
异质生物膜传质模型复制铜绿假单胞菌 PAO1 微菌落中抗生素的外围隔离。
DOI：
10.1101/2023.07.28.551018
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Jones3rd,A-AndrewD
中科院分区：
文献类型：
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作者：
Prince,Joshua;Jones3rd,A-AndrewD
抗生素积累在细菌生物膜小菌落，利用异质性孔隙度和附着位点的配置文件的时空模型复制的周边隔离现象在铜绿假单胞菌PAO1生物膜细胞簇的实验研究报告。这些铜绿假单胞菌细胞簇是在成人囊性纤维化患者中发现的慢性铜绿假单胞菌感染的体外模型，其显示出对抗生素治疗的抗性，导致恶化的发病率和死亡率。这种耐药性部分归因于外周隔离，其中抗生素无法穿透生物膜细胞簇。驱动这种外围隔离的基本物理现象尚未明确确定。本文介绍了数学模型来解释两个提出的物理现象驱动周边封存：生物膜基质附着和体积排除由于可变的生物膜孔隙率。与以前的模型相比，结合这些现象的抗生素积累模型能够更好地拟合观察到的外周隔离数据。
A spatiotemporal model for antibiotic accumulation in bacterial biofilm microcolonies which leverages heterogenous porosity and attachment site profiles replicated the periphery sequestration phenomena reported in prior experimental studies on Pseudomonas aeruginosa PAO1 biofilm cell clusters. These P. aeruginosa cell clusters are in vitro models of the chronic P. aeruginosa infections found in adult cystic fibrosis patients, which display resistance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics are unable to penetrate biofilm cell clusters. The underlying physical phenomena driving this periphery sequestration have not been definitively established. This paper introduces mathematical models to account for two proposed physical phenomena driving periphery sequestration: biofilm matrix attachment and volume-exclusion due to variable biofilm porosity. An antibiotic accumulation model which incorporated these phenomena was able to better fit observed periphery sequestration data compared to previous models.