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J Theor Biol. 2015 Jul 7;376:105-17. doi: 10.1016/j.jtbi.2015.03.031. Epub 2015 Apr 9.

Mathematical model of mycobacterium-host interaction describes physiology of persistence.

Author information

1
International Centre for Genetic Engineering and Biotechnology. Aruna Asaf Ali Marg 110 067, New Delhi, India. Electronic address: gabriele@icgeb.res.in.
2
International Centre for Genetic Engineering and Biotechnology. Aruna Asaf Ali Marg 110 067, New Delhi, India; Translational Health Science and Technology Institute, Drug Discovery Research Centre, Plot No. 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana, India. Electronic address: kanury@icgeb.res.in.
3
Translational Health Science and Technology Institute, Drug Discovery Research Centre, Plot No. 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana, India. Electronic address: samrat.chatterjee@thsti.res.in.

Abstract

Despite extensive studies on the interactions between Mycobacterium tuberculosis (M.tb) and macrophages, the mechanism by which pathogen evades anti-microbial responses and establishes persistence within the host cell remains unknown. In this study, we developed a four-dimensional ODE model to describe the dynamics of host-pathogen interactions in the early phase of macrophage infection. The aim was to characterize the role of host cellular regulators such as iron and lipids, in addition to the bactericidal effector molecule Nitric Oxide. Conditions for existence and stability of the equilibrium point were analysed by examining the behaviour of the model through numerical simulations. These computational investigations revealed that it was the ability of pathogen to interfere with iron and lipid homeostatic pathways of the host cell, which ensured a shift in balance towards pathogen survival and persistence. Interestingly, small perturbations in this equilibrium triggered the cell's bactericidal response, thereby producing an oscillatory dynamic for disease progression.

KEYWORDS:

Differential equations; Host–pathogen interaction; Iron; Lipids; Nitric Oxide

PMID:
25865521
DOI:
10.1016/j.jtbi.2015.03.031
[Indexed for MEDLINE]

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