U.S. Department of Energy

Pacific Northwest National Laboratory

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

TitleSalmonella modulates metabolism during growth under conditions that induce expression of virulence genes.
Publication TypeJournal Article
Year of Publication2013
AuthorsKim Y-M, Schmidt BJ, Kidwai AS, Jones MB, Kaiser BLDeathera, Brewer HM, Mitchell HD, Palsson BO, McDermott JE, Heffron F, Smith RD, Peterson SN, Ansong C, Hyduke DR, Metz TO, Adkins JN
JournalMol Biosyst
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.

DOI10.1039/c3mb25598k
PubMed ID23559334
PubMed Central IDPMC3665296
Grant ListGM085764 / GM / NIGMS NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States
Y01 AI008401 / AI / NIAID NIH HHS / United States
Y1-AI-8401 / AI / NIAID NIH HHS / United States
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