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BACKGROUND An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling(More)
Mycobacterium tuberculosis requires the enzyme isocitrate lyase (ICL) for growth and virulence in vivo. The demonstration that M. tuberculosis also requires ICL for survival during nutrient starvation and has a role during steady state growth in a glycerol limited chemostat indicates a function for this enzyme which extends beyond fat metabolism. As(More)
Mycobacterium tuberculosis infects a third of the world's population. Primary tuberculosis involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which is characterised by slow or non-replicating bacteria. Reactivation of the latent infection involving a switch back to active bacterial replication can lead to(More)
A general paucity of knowledge about the metabolic state of Mycobacterium tuberculosis within the host environment is a major factor impeding development of novel drugs against tuberculosis. Current experimental methods do not allow direct determination of the global metabolic state of a bacterial pathogen in vivo, but the transcriptional activity of all(More)
Computational biologists use network analysis to uncover relationships between various data types of interest for drug discovery. For example, signalling and metabolic pathways are commonly used to understand disease states and drug mechanisms. However, several other flavours of network analysis techniques are also applicable in a drug discovery context.(More)
Mycobacterium tuberculosis requires the enzyme isocitrate lyase (ICL) for growth and virulence in vivo. The demonstration that M. tuberculosis also requires ICL for survival during nutrient starvation and has a role during steady state growth in a glycerol limited chemostat indicates a function for this enzyme which extends beyond fat metabolism. As(More)
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mycobacterium tuberculosis metabolic model <p>GSMN-TB, a genome-scale metabolic model of <it>M. tuberculosis</it>, was constructed and validated using experimental data.</p> Abstract Background: An impediment to the rational development of(More)
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