Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes

Young Mo Kim, Brian J. Schmidt, Afshan S. Kidwai, Marcus B. Jones, B. L. Deatherage Kaiser, Heather M. Brewer, Hugh D. Mitchell, Bernhard O. Palsson, Jason E. McDermott, Fred Heffron, Richard D. Smith, Scott N. Peterson, Charles Ansong, Daniel R. Hyduke, Thomas O. Metz, Joshua N. Adkins

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative pathogen that uses complex mechanisms to invade and proliferate within mammalian host cells. To investigate possible contributions of metabolic processes to virulence in S. Typhimurium grown under conditions known to induce expression of virulence genes, we used a metabolomics-driven systems biology approach coupled with genome-scale modeling. First, we identified distinct metabolite profiles associated with bacteria grown in either rich or virulence-inducing media and report the most comprehensive coverage of the S. Typhimurium metabolome to date. Second, we applied an omics-informed genome-scale modeling analysis of the functional consequences of adaptive alterations in S. Typhimurium metabolism during growth under our conditions. Modeling efforts highlighted a decreased cellular capability to both produce and utilize intracellular amino acids during stationary phase culture in virulence conditions, despite significant abundance increases for these molecules as observed by our metabolomics measurements. Furthermore, analyses of omics data in the context of the metabolic model indicated rewiring of the metabolic network to support pathways associated with virulence. For example, cellular concentrations of polyamines were perturbed, as well as the predicted capacity for secretion and uptake.

    Original languageEnglish (US)
    Pages (from-to)1522-1534
    Number of pages13
    JournalMolecular BioSystems
    Volume9
    Issue number6
    DOIs
    StatePublished - 2013

    Fingerprint

    Salmonella
    Virulence
    Gene Expression
    Growth
    Metabolomics
    Genome
    Salmonella enterica
    Systems Biology
    Metabolome
    Polyamines
    Metabolic Networks and Pathways
    Bacteria
    Amino Acids
    Serogroup

    ASJC Scopus subject areas

    • Biotechnology
    • Molecular Biology
    • Medicine(all)

    Cite this

    Kim, Y. M., Schmidt, B. J., Kidwai, A. S., Jones, M. B., Deatherage Kaiser, B. L., Brewer, H. M., ... Adkins, J. N. (2013). Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes. Molecular BioSystems, 9(6), 1522-1534. https://doi.org/10.1039/c3mb25598k

    Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes. / Kim, Young Mo; Schmidt, Brian J.; Kidwai, Afshan S.; Jones, Marcus B.; Deatherage Kaiser, B. L.; Brewer, Heather M.; Mitchell, Hugh D.; Palsson, Bernhard O.; McDermott, Jason E.; Heffron, Fred; Smith, Richard D.; Peterson, Scott N.; Ansong, Charles; Hyduke, Daniel R.; Metz, Thomas O.; Adkins, Joshua N.

    In: Molecular BioSystems, Vol. 9, No. 6, 2013, p. 1522-1534.

    Research output: Contribution to journalArticle

    Kim, YM, Schmidt, BJ, Kidwai, AS, Jones, MB, Deatherage Kaiser, BL, Brewer, HM, Mitchell, HD, Palsson, BO, McDermott, JE, Heffron, F, Smith, RD, Peterson, SN, Ansong, C, Hyduke, DR, Metz, TO & Adkins, JN 2013, 'Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes', Molecular BioSystems, vol. 9, no. 6, pp. 1522-1534. https://doi.org/10.1039/c3mb25598k
    Kim, Young Mo ; Schmidt, Brian J. ; Kidwai, Afshan S. ; Jones, Marcus B. ; Deatherage Kaiser, B. L. ; Brewer, Heather M. ; Mitchell, Hugh D. ; Palsson, Bernhard O. ; McDermott, Jason E. ; Heffron, Fred ; Smith, Richard D. ; Peterson, Scott N. ; Ansong, Charles ; Hyduke, Daniel R. ; Metz, Thomas O. ; Adkins, Joshua N. / Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes. In: Molecular BioSystems. 2013 ; Vol. 9, No. 6. pp. 1522-1534.
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    abstract = "Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative pathogen that uses complex mechanisms to invade and proliferate within mammalian host cells. To investigate possible contributions of metabolic processes to virulence in S. Typhimurium grown under conditions known to induce expression of virulence genes, we used a metabolomics-driven systems biology approach coupled with genome-scale modeling. First, we identified distinct metabolite profiles associated with bacteria grown in either rich or virulence-inducing media and report the most comprehensive coverage of the S. Typhimurium metabolome to date. Second, we applied an omics-informed genome-scale modeling analysis of the functional consequences of adaptive alterations in S. Typhimurium metabolism during growth under our conditions. Modeling efforts highlighted a decreased cellular capability to both produce and utilize intracellular amino acids during stationary phase culture in virulence conditions, despite significant abundance increases for these molecules as observed by our metabolomics measurements. Furthermore, analyses of omics data in the context of the metabolic model indicated rewiring of the metabolic network to support pathways associated with virulence. For example, cellular concentrations of polyamines were perturbed, as well as the predicted capacity for secretion and uptake.",
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