Mathematical model of mycobacterium–host interaction describes physiology of persistence. (7th July 2015)

• Record Type: Journal Article
• Authors: Pedruzzi, Gabriele; Rao, Kanury V.S.; Chatterjee, Samrat
• Is Part Of: Journal of theoretical biology. Volume 376(2015)
• Page Start: 105
• Page End: 117
• Publication Date: 2015-07-07
• Subjects: Host–pathogen interaction -- Differential equations -- Iron -- Lipids -- Nitric Oxide; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2015.03.031
• Languages: English
• ISSNs: 0022-5193

Abstract

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. Abstract : Author-Highlights: A delicate balance underlies the persistence of Mycobacterium tuberculosis infection. The pathogen exploits the iron homeostasis to hamper host immune response. Manipulation of lipid metabolism is a favourite strategy for slow-growing bacteria.