title: 13C-flux spectral analysis of host-pathogen metabolism reveals a mixed diet for intracellular Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: Dany J V
authors.initials: DJ
authors.lastname: Beste
authors.forename: Katharina
authors.initials: K
authors.lastname: Nöh
authors.forename: Sebastian
authors.initials: S
authors.lastname: Niedenführ
authors.forename: Tom A
authors.initials: TA
authors.lastname: Mendum
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Hawkins
authors.forename: Jane L
authors.initials: JL
authors.lastname: Ward
authors.forename: Michael H
authors.initials: MH
authors.lastname: Beale
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wiechert
authors.forename: Johnjoe
authors.initials: J
authors.lastname: McFadden
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D002244:Carbon / Q000032:analysis / Q000378:metabolism*; D002247:Carbon Isotopes / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000596:Amino Acids; D002247:Carbon Isotopes; D002244:Carbon
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