Summary of project PR000350

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000350. The data can be accessed directly via it's Project DOI: 10.21228/M8T30C This work is supported by NIH grant, U2C- DK119886.


Project ID: PR000350
Project DOI:doi: 10.21228/M8T30C
Project Title:Metabolic Adaptation of Staphylococcus aureus to Host Immunity
Project Summary:Staphylococcus aureus infections are difficult to treat given the drug-resistant nature of this bacterium. Methicillin-Resistant Staphylococcus aureus (MRSA) is considered the single most deadly bacterial infection in the United States. The bacterium resists nearly every aspect of innate immunity, including the cytotoxic effects of nitric oxide (NO?) which is an innate immune effector produced by phagocytes in response to infection. NO? interferes with various metabolic pathways in pathogens by reacting with redox centers of multiple enzymes. We have demonstrated that S. aureus NO?-resistance is essential for full virulence. We have also shown that S. aureus NO-resistance is predicated on the abundance of glucose, which may explain exacerbated S. aureus disease outcomes associated with diabetic patients having poorly controlled blood sugar. Here we propose to employ metabolomics to probe the nature of the S. aureus NO-resistant metabolic state. We will thereby bridge a fundamental gap in our knowledge of S. aureus pathogenesis by defining metabolic pathways essential to cause disease in immunocompetent hosts. These key metabolic pathways represent important therapeutic targets for future research. Define the requirement for glycolytic carbon/energy sources for the S. aureus NO-RMS: While S. aureus can thrive on a variety of gluconeogenic carbon sources (e.g. amino acids, glycerol, lactate etc.), none of these are capable of supporting NO?-resistance. We will compare changes in intracellular metabolites in cells growing on gluconeogenic carbon sources following NO?-exposure to elucidate what features of gluconeogenesis are incompatible with NO?-resistance. The absolute requirement for glycolytic carbon sources for NO-resistance is interesting given the disproportionately poor disease outcomes of MRSA infections in diabetic patients with elevated blood glucose.
Institute:University of North Carolina at Chapel Hill
Department:Department of Microbiology and Immnunology, UNC-CH
Last Name:Richardson
First Name:Anthony
Address:125 Mason Farm Rd, Marsico Hall 6209, Chapel Hill, NC 27599

Summary of all studies in project PR000350

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST000453 Metabolic Adaptation of Staphylococcus aureus to Host Immunity Staphylococcus aureus University of North Carolina MS* 2017-10-03 1 92 Uploaded data (131G)*