Rule Based Modeling of Iron Homeostasis in Tuberculosis
Conference poster, 2010
Mycobacterium tuberculosis (Mtb), which causes Tuberculosis (TB), has evolved into many
drug resistant forms, and in symbiosis with AIDS and other diseases, has become a dreaded
pathogen world-wide. In an attempt to find new drugs, researchers have turned to the study of
iron homeostasis in TB: iron is an important resource that Mtb steals from its host, and is
involved in the manifestation of virulence. We have formally encoded the relevant molecular
interactions described in the literature, yielding a program to simulate these aspects of iron
metabolism in Mtb, in the host, and in the interaction between the two. Iron acquisition via
siderophores is featured in detail.
The Kappa modeling language we use represents molecular interactions compactly by rules,
these being generalisations of chemical equations. The Kappa tool tells us syntactically how
the reactions are related, so we can see which play a central role, and which are comparatively
isolated. Our simulation results, both pathways and concentrations of species, match those
described in the literature. Our program can therefore be used as an unambiguous
representation to anchor discussions about iron and TB, and to predict the results of
hypothetical perturbations that might be of use in the search for new drugs. For example, the
results of changing the infection level are as expected.
A future possibility would be to combine our model with a genetic algorithm to suggest ways
in which Mtb might evolve resistance to planned interventions.