Modelling the effects of bacterial cell state and spatial location on tuberculosis treatment: Insights from a hybrid multiscale cellular automaton model.
Modelling the effects of bacterial cell state and spatial location on tuberculosis treatment: Insights from a hybrid multiscale cellular automaton model.
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DOI：
10.1016/j.jtbi.2018.03.006
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发表时间：
2018-06-07
影响因子：
2
通讯作者：
Gillespie SH
中科院分区：
文献类型：
--
作者：
Bowness R;Chaplain MAJ;Powathil GG;Gillespie SH
基于个体的结核病进展和治疗模型。不同的结核菌表型如何影响治疗结果。结核杆菌空间分布对治疗效果的影响。如果要改善结核病（TB）治疗，就需要增加对肺部疾病的了解。研究表明，与脂质体的存在相关的代谢活性较低的细菌对抗生素不太敏感，最近的结果突出了不同化合物在病变中的浓度差异。因此，治疗的成功关键取决于构成感染的单个细菌的反应。我们提出了一种混合的，基于个人的方法，分析时空动态在细胞水平上，连接的行为，个别细菌和宿主细胞的宏观行为的微环境。单个元素（细菌，巨噬细胞和T细胞）使用元胞自动机（CA）规则建模，并纳入氧气，药物和趋化因子动力学的演变，以研究病理病变中微环境的影响。我们允许细菌根据氧气浓度转换状态，这会影响它们对治疗的反应。这是第一个多尺度模型的类型，考虑氧气驱动的结核分枝杆菌和抗生素治疗的表型转换。使用这个模型，我们调查细菌细胞状态和初始细菌位置对治疗结果的作用。我们证明，当细菌位于离血管更远的地方时，更有可能出现不太有利的结果，即感染被控制/清除之前的时间更长，治疗失败或后来复发。我们还表明，在模拟结束时细菌仍然存在的情况下，生物体往往生长缓慢，通常位于肉芽肿内，周围是干酪样物质。
Individual-based model of tuberculosis disease progression and treatment. How different tuberculosis bacterial phenotypes affect treatment outcome. The effect of spatial distribution of tuberculosis bacilli on treatment outcome. If improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of different compounds into lesions. Treatment success therefore depends critically on the responses of the individual bacteria that constitute the infection. 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.
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影响因子：
6.4
作者：
Keren I;Minami S;Rubin E;Lewis K
通讯作者：
Lewis K
影响因子：
5.2
作者：
Hammond, Robert J. H.;Baron, Vincent O.;Gillespie, Stephen H.
通讯作者：
Gillespie, Stephen H.
影响因子：
4.6
作者：
Aljayyoussi G;Jenkins VA;Sharma R;Ardrey A;Donnellan S;Ward SA;Biagini GA
通讯作者：
Biagini GA
影响因子：
3.5
作者：
Dasu, A;Toma-Dasu, I;Karlsson, M
通讯作者：
Karlsson, M
影响因子：
3.7
作者：
Asefa, Anteneh;Teshome, Wondu
通讯作者：
Teshome, Wondu