Jump to main content
Jump to site search

Issue 10, 2011
Previous Article Next Article

Rule-based modelling of iron homeostasis in tuberculosis

Author affiliations

Abstract

To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and maintaining the required concentration of iron becomes a matter of contest between the host and the pathogen, both trying to achieve this through complex molecular networks. The extent of complexity makes it important to obtain a systems perspective of the interplay between the host and the pathogen with respect to iron homeostasis. We have reconstructed a systems model comprising 92 components and 85 proteinprotein or protein–metabolite interactions, which have been captured as a set of 194 rules. Apart from the interactions, these rules also account for protein synthesis and decay, RBC circulation and bacterial production and death rates. We have used a rule-based modelling approach, Kappa, to simulate the system separately under infection and non-infection conditions. Various perturbations including knock-outs and dual perturbation were also carried out to monitor the behavioral change of important proteins and metabolites. From this, key components as well as the required controlling factors in the model that are critical for maintaining iron homeostasis were identified. The model is able to re-establish the importance of iron-dependent regulator (ideR) in Mtb and transferrin (Tf) in the host. Perturbations, where iron storage is increased, appear to enhance nutritional immunity and the analysis indicates how they can be harmful for the host. Instead, decreasing the rate of iron uptake by Tf may prove to be helpful. Simulation and perturbation studies help in identifying Tf as a possible drug target. Regulating the mycobactin (myB) concentration was also identified as a possible strategy to control bacterial growth. The simulations thus provide significant insight into iron homeostasis and also for identifying possible drug targets for tuberculosis.

Graphical abstract: Rule-based modelling of iron homeostasis in tuberculosis

Back to tab navigation

Supplementary files

Publication details

The article was received on 05 Mar 2011, accepted on 18 Jul 2011 and first published on 11 Aug 2011


Article type: Paper
DOI: 10.1039/C1MB05093A
Mol. BioSyst., 2011,7, 2750-2768

  •   Request permissions

    Rule-based modelling of iron homeostasis in tuberculosis

    S. Ghosh, K. V. S. Prasad, S. Vishveshwara and N. Chandra, Mol. BioSyst., 2011, 7, 2750
    DOI: 10.1039/C1MB05093A

Search articles by author

Spotlight

Advertisements