title: Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes.
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.
authors.affiliation: Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Young-Mo
authors.initials: YM
authors.lastname: Kim
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Schmidt
authors.forename: Afshan S
authors.initials: AS
authors.lastname: Kidwai
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Deatherage Kaiser
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brewer
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Mitchell
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.forename: Fred
authors.initials: F
authors.lastname: Heffron
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: Charles
authors.initials: C
authors.lastname: Ansong
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Hyduke
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D011073:Polyamines / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D011073:Polyamines; D037521:Virulence Factors
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