Journal
CHEMISTRY & BIOLOGY
Volume 20, Issue 8, Pages 1012-1021Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2013.06.012
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Funding
- Wellcome Trust [088677]
- Biotechnology and Biological Sciences Research Council [MET20482, BB/D525121/1] Funding Source: researchfish
- BBSRC [BB/D525121/1] Funding Source: UKRI
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Whereas intracellular carbon metabolism has emerged as an attractive drug target, the carbon sources of intracellularly replicating pathogens, such as the tuberculosis bacillus Mycobacterium tuberculosis, which causes long-term infections in one-third of the world's population, remain mostly unknown. We used a systems-based approach-C-13-flux spectral analysis (FSA) complemented with manual analysis to measure the metabolic interaction between M. tuberculosis and its macrophage host cell. C-13-FSA analysis of experimental data showed that M. tuberculosis obtains a mixture of amino acids, C-1 and C-2 substrates from its host cell. We experimentally confirmed that the C-1 substrate was derived from CO2. C-13 labeling experiments performed on a phosphoenolpyruvate carboxykinase mutant revealed that intracellular M. tuberculosis has access to glycolytic C-3 substrates. These findings provide constraints for developing novel chemotherapeutics.
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