Summary of project PR000786

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 PR000786. The data can be accessed directly via it's Project DOI: 10.21228/M83398 This work is supported by NIH grant, U2C- DK119886.


Project ID: PR000786
Project DOI:doi: 10.21228/M83398
Project Title:The ClpCP complex modulates respiratory, but not fermentative, metabolism in Staphylococcus aureus and is regulated in a SrrAB-dependent manner.
Project Summary:The staphylococcal respiratory regulator (SrrAB) modulates energy metabolism in Staphylococcus aureus. Studies have suggested that regulated protein catabolism facilitates energy homeostasis. Regulated proteolysis in S. aureus is achieved through protein complexes composed of a peptidase (ClpQ or ClpP) in association with an AAA+ family ATPase (typically ClpC or ClpX). In the current report, we tested the hypothesis that SrrAB regulates a Clp complex to facilitate energy homeostasis in S. aureus. Strains deficient in one or more Clp complexes are attenuated for growth in the presence of puromycin, which causes enrichment of misfolded proteins. A ΔsrrAB strain had increased sensitivity to puromycin. Epistasis experiments suggested that the puromycin sensitivity phenotype of the ΔsrrAB strain was a result of decreased ClpC activity. Consistent with this, transcriptional activity of clpC was decreased in the ΔsrrAB mutant and overexpression of clpC suppressed the puromycin sensitivity of the ΔsrrAB strain. Genetic studies suggested that phosphorylated SrrA is required to influence puromycin resistance. ClpC positively influenced respiration in association with ClpP. ClpP was also required for optimal fermentative growth, whereas ClpC was dispensable. Metabolomics studies demonstrated that intracellular metabolic profiles of the ΔclpC and ΔsrrAB mutants are distinct from the wild type strain, supporting the notion that both ClpC and SrrAB affect central metabolism. We propose a model wherein SrrAB regulates energy homeostasis, in part, via modulation of regulated proteolysis.
Institute:Montana State University
Department:Chemistry and Biochemistry
Laboratory:Copie Lab
Last Name:Eilers
First Name:Brian
Address:103 Chemistry and Biochemistry Bldg, RM 144, Valerie Copie Lab, Bozeman, Montana, 59717, USA
Publications:Journal of Bacteriology (accepted with revisions)

Summary of all studies in project PR000786

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST001174 Role of ClpCP in respiratory and fermentative growth Staphylococcus aureus Montana State University NMR 2019-05-15 1 16 Uploaded data (8.4M)*