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小鼠胃肠道感染中细菌种群动态的计算模型

A Computational Model of Bacterial Population Dynamics in Gastrointestinal Infections in Mice.

作者信息

Geißert Janina K, Bohn Erwin, Mostolizadeh Reihaneh, Dräger Andreas, Autenrieth Ingo B, Beier Sina, Deusch Oliver, Renz Alina, Eichner Martin, Schütz Monika S

机构信息

Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.

Computational Systems Biology of Infections and Antimicrobial-Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, Sand 14, 72076 Tübingen, Germany.

出版信息

Biology (Basel). 2022 Feb 12;11(2):297. doi: 10.3390/biology11020297.

Abstract

The complex interplay of a pathogen with its virulence and fitness factors, the host's immune response, and the endogenous microbiome determine the course and outcome of gastrointestinal infection. The expansion of a pathogen within the gastrointestinal tract implies an increased risk of developing severe systemic infections, especially in dysbiotic or immunocompromised individuals. We developed a mechanistic computational model that calculates and simulates such scenarios, based on an ordinary differential equation system, to explain the bacterial population dynamics during gastrointestinal infection. For implementing the model and estimating its parameters, oral mouse infection experiments with the enteropathogen, (Ye), were carried out. Our model accounts for specific pathogen characteristics and is intended to reflect scenarios where colonization resistance, mediated by the endogenous microbiome, is lacking, or where the immune response is partially impaired. Fitting our data from experimental mouse infections, we can justify our model setup and deduce cues for further model improvement. The model is freely available, in SBML format, from the BioModels Database under the accession number MODEL2002070001.

摘要

病原体与其毒力和适应性因子、宿主免疫反应以及内源性微生物群之间复杂的相互作用,决定了胃肠道感染的病程和结果。病原体在胃肠道内的扩散意味着发生严重全身感染的风险增加,尤其是在生态失调或免疫功能低下的个体中。我们基于常微分方程系统开发了一个机械计算模型,用于计算和模拟此类情况,以解释胃肠道感染期间的细菌种群动态。为了实现该模型并估计其参数,我们用肠道病原体(Ye)进行了口服小鼠感染实验。我们的模型考虑了特定病原体的特征,旨在反映内源性微生物群介导的定植抗性缺乏或免疫反应部分受损的情况。通过拟合实验小鼠感染的数据,我们可以证明模型设置的合理性,并推断出进一步改进模型的线索。该模型以SBML格式免费提供,可从BioModels数据库获取,登录号为MODEL2002070001。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db9c/8869254/0d2e75a01a8b/biology-11-00297-g001.jpg

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