论文标题
在存在扩散和吸收障碍的情况下,抗生素通过生物膜扩散
Diffusion of antibiotics through a biofilm in the presence of diffusion and absorption barriers
论文作者
论文摘要
当生物膜中发生扩散和/或吸收屏障时,我们提出了通过细菌生物膜的抗生素扩散模型。该模型的想法是:我们根据探测外部区域的扩散,在一种媒介中推断出扩散过程的细节。由于生物膜具有类似凝胶的稠度,因此我们假设可能会发生生物膜中颗粒的细胞扩散。为了描述这个过程,我们使用具有可调异常扩散指数的分数亚缩放 - 吸收方程。生物膜边界处的边界条件是通过粒子随机行走模型在离散晶格上得出的,导致涉及分数时间衍生物的表达。我们表明,通过生物膜扩散的物质的时间演变明确取决于生物膜中是否存在抗生素吸收。该事实用于实验检查生物膜中的抗生素吸收,以及生物膜参数是否随时间变化。我们根据上述物理特征提出了生物膜中抗生素扩散的四阶段模型。讨论了对阶段的生物学解释,特别是它们与细菌防御机制的关系。将理论结果与通过铜绿假单胞菌生物膜的环丙沙星扩散的经验结果,以及通过米拉比利斯生物膜的环丙沙星和庆大霉素扩散的经验结果。
We propose a model of antibiotic diffusion through a bacterial biofilm when diffusion and/or absorption barriers develop in the biofilm. The idea of this model is: We deduce details of the diffusion process in a medium in which direct experimental study is difficult, based on probing diffusion in external regions. Since a biofilm has a gel-like consistency, we suppose that subdiffusion of particles in the biofilm may occur. To describe this process we use a fractional subdiffusion-absorption equation with an adjustable anomalous diffusion exponent. The boundary conditions at the boundaries of the biofilm are derived by means of a particle random walk model on a discrete lattice leading to an expression involving a fractional time derivative. We show that the temporal evolution of the total amount of substance that has diffused through the biofilm explicitly depends on whether there is antibiotic absorption in the biofilm. This fact is used to experimentally check for antibiotic absorption in the biofilm and if the biofilm parameters change over time. We propose a four-stage model of antibiotic diffusion in biofilm based on the mentioned above physical characteristics. The biological interpretation of the stages, in particular their relation with the bacterial defence mechanisms, is discussed. Theoretical results are compared with empirical results of ciprofloxacin diffusion through Pseudomonas aeruginosa biofilm, and ciprofloxacin and gentamicin diffusion through Proteus mirabilis biofilm.