Prince Joshua, Jones A-Andrew D
Department of Civil and Environmental Engineering, Duke University.
Integrated Toxicology and Environmental Health Program, Duke University.
bioRxiv. 2023 Jul 29:2023.07.28.551018. doi: 10.1101/2023.07.28.551018.
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 biofilm cell clusters. These cell clusters are models of the chronic 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.
一种利用异质孔隙率和附着位点分布的细菌生物膜微菌落中抗生素积累的时空模型，重现了先前关于生物膜细胞簇的实验研究中报道的外周隔离现象。这些细胞簇是成年囊性纤维化患者慢性感染的模型，表现出对抗生素治疗的抗性，导致发病率和死亡率加剧。这种抗性部分归因于外周隔离，即抗生素无法穿透生物膜细胞簇。驱动这种外周隔离的潜在物理现象尚未明确确定。本文引入数学模型来解释驱动外周隔离的两种提出的物理现象：生物膜基质附着和由于可变生物膜孔隙率导致的体积排斥。与先前的模型相比，纳入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。
