Heterogenous biofilm mass-transport model replicates periphery sequestration of antibiotics in Pseudomonas aeruginosa PAO1 microcolonies.

Heterogenous biofilm mass-transport model replicates periphery sequestration of antibiotics in Pseudomonas aeruginosa PAO1 microcolonies.
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异质生物被膜传质模型再现了铜绿假单胞菌PAO1微菌落中抗生素在周边区域的隔离现象。

DOI:
10.1073/pnas.2312995120
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发表时间:
2023-11-21
影响因子:
11.1
通讯作者:
Jones III, A-Andrew D.
Jones III, A-Andrew D.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Prince, Joshua;Jones III, A-Andrew D.

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利用异质性孔隙率和附着位点分布的细菌生物膜小菌落中抗生素积累的模型复制了在铜绿假单胞菌PAO1生物膜细胞簇的先前实验研究中报道的外围隔离。这些铜绿假单胞菌细胞簇是囊性纤维化患者中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耐受性,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更好地拟合观察到的外周隔离数据。
A model for antibiotic accumulation in bacterial biofilm microcolonies utilizing heterogenous porosity and attachment site profiles replicated the periphery sequestration 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 in cystic fibrosis patients which display recalcitrance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics fail to penetrate biofilm cell clusters. The 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 better fit observed periphery sequestration data compared to previous models.
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