Study of the bioenergetics to identify the novel pathways as a drug target against Mycobacterium tuberculosis using Petri net

Abstract

Tuberculosis is one of the life-threatening diseases globally, caused by the bacteria Mycobacterium tuberculosis. In order to control this epidemic globally, there is an urgent need to discover new drugs with novel mechanism of action that can help in shortening the duration of treatment for both drug resistant and drug sensitive tuberculosis. Mycobacterium essentially depends on oxidative phosphorylation for its growth and establishment of pathogenesis. This pathway is unique in Mycobacterium tuberculosis as compared to host due to the differences in some of the enzyme complexes carrying electron transfer. Hence, it serves as an important drug target area. The uncouplers which inhibit adenosine triphosphate synthesis, could play a vital role in serving as antimycobacterial agents and thus could help in eradicating this deadly disease. In this article, the bioenergetics of Mycobacterium tuberculosis are studied with and without uncouplers using Petri net. Petri net is among the most widely used mathematical and computational tools to model and study the complex biochemical networks. We first represented the bioenergetic pathway as a Petri net which is then validated and analyzed using invariant analysis techniques of Petri net. The valid mathematical models presented here are capable to explain the molecular mechanism of uncouplers and the processes occurring within the electron transport chain of Mycobacterium tuberculosis. The results explained the net behavior in agreement with the biological results and also suggested some possible processes and pathways to be studied as a drug target for developing antimycobacterials.