(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
Divisions :	Surrey research (other units)
Authors :	Name Email ORCID Beste, DJ d.beste@surrey.ac.uk Nöh, K Niedenführ, S Mendum, TA t.mendum@surrey.ac.uk Hawkins, ND Ward, JL Beale, MH Wiechert, W McFadden, J j.mcfadden@surrey.ac.uk
Date :	31 July 2013
DOI :	10.1016/j.chembiol.2013.06.012
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 09:56
Last Modified :	24 Jan 2020 18:03
URI:	http://epubs.surrey.ac.uk/id/eprint/825706

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