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(13)C-Flux Spectral Analysis of Host-Pathogen Metabolism Reveals a Mixed Diet for Intracellular Mycobacterium tuberculosis.

Beste, DJ, Nöh, K, Niedenführ, S, Mendum, TA, Hawkins, ND, Ward, JL, Beale, MH, Wiechert, W and McFadden, J (2013) (13)C-Flux Spectral Analysis of Host-Pathogen Metabolism Reveals a Mixed Diet for Intracellular Mycobacterium tuberculosis. Chem Biol, 20 (8). pp. 1012-1021.

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Abstract

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-(13)C-flux spectral analysis (FSA) complemented with manual analysis-to measure the metabolic interaction between M. tuberculosis and its macrophage host cell. (13)C-FSA analysis of experimental data showed that M. tuberculosis obtains a mixture of amino acids, C1 and C2 substrates from its host cell. We experimentally confirmed that the C1 substrate was derived from CO2. (13)C labeling experiments performed on a phosphoenolpyruvate carboxykinase mutant revealed that intracellular M. tuberculosis has access to glycolytic C3 substrates. These findings provide constraints for developing novel chemotherapeutics.

Item Type: Article
Authors :
NameEmailORCID
Beste, DJd.beste@surrey.ac.ukUNSPECIFIED
Nöh, KUNSPECIFIEDUNSPECIFIED
Niedenführ, SUNSPECIFIEDUNSPECIFIED
Mendum, TAt.mendum@surrey.ac.ukUNSPECIFIED
Hawkins, NDUNSPECIFIEDUNSPECIFIED
Ward, JLUNSPECIFIEDUNSPECIFIED
Beale, MHUNSPECIFIEDUNSPECIFIED
Wiechert, WUNSPECIFIEDUNSPECIFIED
McFadden, Jj.mcfadden@surrey.ac.ukUNSPECIFIED
Date : 31 July 2013
Identification Number : https://doi.org/10.1016/j.chembiol.2013.06.012
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:56
Last Modified : 17 May 2017 14:45
URI: http://epubs.surrey.ac.uk/id/eprint/825706

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