title: NMR analysis of a stress response metabolic signaling network.
abstract: We previously hypothesized that Staphylococcus epidermidis senses a diverse set of environmental and nutritional factors associated with biofilm formation through a modulation in the activity of the tricarboxylic acid (TCA) cycle. Herein, we report our further investigation of the impact of additional environmental stress factors on TCA cycle activity and provide a detailed description of our NMR methodology. S. epidermidis wild-type strain 1457 was treated with stressors that are associated with biofilm formation, a sublethal dose of tetracycline, 5% NaCl, 2% glucose, and autoinducer-2 (AI-2). As controls and to integrate our current data with our previous study, 4% ethanol stress and iron-limitation were also used. Consistent with our prior observations, the effect of many environmental stress factors on the S. epidermidis metabolome was essentially identical to the effect of TCA cycle inactivation in the aconitase mutant strain 1457-acnA::tetM. A detailed quantitative analysis of metabolite concentration changes using 2D (1)H-(13)C HSQC and (1)H-(1)H TOCSY spectra identified a network of 37 metabolites uniformly affected by the stressors and TCA cycle inactivation. We postulate that the TCA cycle acts as the central pathway in a metabolic signaling network.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Steven
authors.initials: S
authors.lastname: Halouska
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schiaffo
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
mesh_terms: D018441:Biofilms; D002952:Citric Acid Cycle; D055442:Metabolome; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D025341:Principal Component Analysis; D015398:Signal Transduction; D013212:Staphylococcus epidermidis / Q000254:growth & development / Q000378:metabolism*