A systematic evaluation of Mycobacterium tuberculosis Genome-Scale Metabolic Networks

摘要

The tuberculosis bacillus, Mycobacterium tuberculosis (Mtb), is a global killer causing millions of deaths every year and is therefore a major burden to human health. Treatment of tuberculosis requires a cocktail of antibiotics for a minimum of 6 months. Treatment failure is common and is a major driver in the upward trend of antibiotic resistance, recognized by the World Health Organization as one of top ten threats to global health. A key to the success of Mtb as a human pathogen is ascribed to its extraordinary metabolic flexibility. Understanding the metabolism of Mtb is therefore an important goal of TB researchers as metabolic pathways present attractive drug targets. A powerful approach to study metabolism is through the use of genome-scale metabolic networks which enable metabolism to be studied at the whole system level rather than one enzyme at a time. Here, we comprehensively compare available genome scale metabolic networks. Our results identify the best performing networks for a variety of modelling approaches. This work allowed us to refine these models for the TB community to use in future studies to probe the metabolism of this formidable human pathogen.