Kinetic modeling of' Toxoplasma gondii invasion
Kinetic modeling of' Toxoplasma gondii invasion
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DOI：
10.1016/j.jtbi.2007.09.008
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发表时间：
2007-12-21
影响因子：
2
通讯作者：
Pineda, Fernando J.
中科院分区：
文献类型：
--
作者：
Kafsack, Bjoern F. C.;Carruthers, Vern B.;Pineda, Fernando J.
顶复门包括负责全球性疾病如疟疾、隐孢子虫病和弓形虫病的寄生虫。寄生虫在宿主的细胞内繁殖，使入侵宿主细胞成为其生命周期的重要步骤。表征宿主细胞入侵的阶段，传统上涉及随着时间的推移对单个寄生虫进行繁琐的显微镜观察。作为一种替代方案，我们介绍了使用隔间模型来解释从入侵寄生虫的同步种群的快照收集的数据。模型的参数估计通过最大负对数似然原理。估计参数值及其95%置信区间（95% CI）与报告的个体寄生虫观察结果一致。对于RH株寄生虫，我们的模型得出：（1）穿透宿主细胞质膜需要26 s（95%，Cl：22-30 s）;（2）最终侵入的寄生虫保持附着的时间是最终从宿主细胞分离的寄生虫的三倍，以及（3）25%（95%Cl：19-33%）的寄生虫侵入，而75%（95%Cl：67- 81%）的寄生虫最终从其宿主细胞脱离而不进行侵入。该模型的一个主要特点是纳入了无法直接观察到的入侵阶段。这使我们能够表征寄生虫从宿主细胞脱离的现象。如果没有数学模型，这种现象的性质很难量化。我们的结论是，数学建模提供了一个强大的新工具，表征宿主细胞入侵细胞内寄生虫的阶段。(c)2007爱思唯尔有限公司保留所有权利。
The phylum Apicomplexa includes parasites responsible for global scourges such as malaria, cryptosporidiosis, and toxoplasmosis. Parasites in this phylum reproduce inside the cells of their hosts, making invasion of host cells an essential step of their life cycle. Characterizing the stages of host-cell invasion, has traditionally involved tedious microscopic observations of individual parasites over time. As an alternative, we introduce the use of compartment models for interpreting data collected from snapshots of synchronized populations of invading parasites. Parameters of the model are estimated via a maximum negative log-likelihood principle. Estimated parameter values and their 95% confidence intervals (95% Cl), are consistent with reported observations of individual parasites. For RH strain parasites, our model yields that: ( 1) penetration of the host-cell plasma membrane takes 26 s (95%, Cl: 22-30 s); (2) parasites that ultimately invade, remain attached three times longer than parasites that eventually detach from the host cells, and (3) 25% (95% Cl: 19-33%) of parasites invade while 75% (95% Cl: 67-81 %) eventually detach from their host cells without progressing to invasion. A key feature of the model is the incorporation of invasion stages that cannot be directly observed. This allows us to characterize the phenomenon of parasite detachment from host cells. The properties of this phenomenon would be difficult to quantity without a mathematical model. We conclude that mathematical modeling provides a powerful new tool for characterizing the stages of host-cell invasion by intracellular parasites. (c) 2007 Elsevier Ltd. All rights reserved.