کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8876729 1623764 2018 21 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modelling the effects of bacterial cell state and spatial location on tuberculosis treatment: Insights from a hybrid multiscale cellular automaton model
ترجمه فارسی عنوان
مدل سازی اثرات وضعیت سلول های باکتریایی و مکان فضایی برای درمان سل: بینش یک مدل اتوماتیک چند سلولی
کلمات کلیدی
بیماری سل، خودکار سلولی، مدل چندبعدی هیبرید، آنتی بیوتیک ها، باکتری،
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی
We propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the cellular level, linking the behaviour of individual bacteria and host cells with the macroscopic behaviour of the microenvironment. The individual elements (bacteria, macrophages and T cells) are modelled using cellular automaton (CA) rules, and the evolution of oxygen, drugs and chemokine dynamics are incorporated in order to study the effects of the microenvironment in the pathological lesion. We allow bacteria to switch states depending on oxygen concentration, which affects how they respond to treatment. This is the first multiscale model of its type to consider both oxygen-driven phenotypic switching of the Mycobacterium tuberculosis and antibiotic treatment. Using this model, we investigate the role of bacterial cell state and of initial bacterial location on treatment outcome. We demonstrate that when bacteria are located further away from blood vessels, less favourable outcomes are more likely, i.e. longer time before infection is contained/cleared, treatment failure or later relapse. We also show that in cases where bacteria remain at the end of simulations, the organisms tend to be slower-growing and are often located within granulomas, surrounded by caseous material.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 446, 7 June 2018, Pages 87-100
نویسندگان
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