Catabolite control protein E (CcpE) is a LysR-type transcriptional regulator of tricarboxylic acid cycle activity in Staphylococcus aureus

J Biol Chem. 2013 Dec 13;288(50):36116-28. doi: 10.1074/jbc.M113.516302. Epub 2013 Nov 5.


The tricarboxylic acid cycle (TCA cycle) is a central metabolic pathway that provides energy, reducing potential, and biosynthetic intermediates. In Staphylococcus aureus, TCA cycle activity is controlled by several regulators (e.g. CcpA, CodY, and RpiRc) in response to the availability of sugars, amino acids, and environmental stress. Developing a bioinformatic search for additional carbon catabolite-responsive regulators in S. aureus, we identified a LysR-type regulator, catabolite control protein E (CcpE), with homology to the Bacillus subtilis CcpC regulator. Inactivation of ccpE in S. aureus strain Newman revealed that CcpE is a positive transcriptional effector of the first two enzymes of the TCA cycle, aconitase (citB) and to a lesser extent citrate synthase (citZ). Consistent with the transcriptional data, aconitase activity dramatically decreased in the ccpE mutant relative to the wild-type strain. The effect of ccpE inactivation on citB transcription and the lesser effect on citZ transcription were also reflected in electrophoretic mobility shift assays where CcpE bound to the citB promoter but not the citZ promoter. Metabolomic studies showed that inactivation of ccpE resulted in increased intracellular concentrations of acetate, citrate, lactate, and alanine, consistent with a redirection of carbon away from the TCA cycle. Taken together, our data suggest that CcpE is a major direct positive regulator of the TCA cycle gene citB.

Keywords: Bacterial Metabolism; Metabolic Regulation; Staphylococcus aureus; Transcription Regulation; Tricarboxylic Acid (TCA) Cycle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Citric Acid Cycle / genetics*
  • Gene Deletion
  • Genetic Loci / genetics
  • Metabolome
  • Molecular Sequence Data
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic*


  • Bacterial Proteins
  • Repressor Proteins
  • Transcription Factors
  • catabolite control proteins, bacteria
  • LysR protein, Bacteria