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

Torsten Hartmann, Bo Zhang, Grégory Baronian, Bettina Schulthess, Dagmar Homerova, Stephanie Grubmul̈ler, Erika Kutzner, Rosmarie Gaupp, Ralph Bertram, Robert Powers, Wolfgang Eisenreich, Jan Kormanec, Mathias Herrmann, Virginie Molle, Greg A Somerville, Markus Bischoff

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)36116-36128
Number of pages13
JournalJournal of Biological Chemistry
Volume288
Issue number50
DOIs
StatePublished - Dec 13 2013

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Citric Acid Cycle
Staphylococcus aureus
Aconitate Hydratase
Transcription
Proteins
Carbon
Cyclic AMP Receptor Protein
Sugar Acids
Citrate (si)-Synthase
Electrophoretic mobility
Metabolomics
Electrophoretic Mobility Shift Assay
Bacilli
Bioinformatics
Metabolic Networks and Pathways
Bacillus subtilis
Computational Biology
Citric Acid
Sugars
Alanine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Catabolite control protein E (CcpE) is a LysR-type transcriptional regulator of tricarboxylic acid cycle activity in Staphylococcus aureus. / Hartmann, Torsten; Zhang, Bo; Baronian, Grégory; Schulthess, Bettina; Homerova, Dagmar; Grubmul̈ler, Stephanie; Kutzner, Erika; Gaupp, Rosmarie; Bertram, Ralph; Powers, Robert; Eisenreich, Wolfgang; Kormanec, Jan; Herrmann, Mathias; Molle, Virginie; Somerville, Greg A; Bischoff, Markus.

In: Journal of Biological Chemistry, Vol. 288, No. 50, 13.12.2013, p. 36116-36128.

Research output: Contribution to journalArticle

Hartmann, T, Zhang, B, Baronian, G, Schulthess, B, Homerova, D, Grubmul̈ler, S, Kutzner, E, Gaupp, R, Bertram, R, Powers, R, Eisenreich, W, Kormanec, J, Herrmann, M, Molle, V, Somerville, GA & Bischoff, M 2013, 'Catabolite control protein E (CcpE) is a LysR-type transcriptional regulator of tricarboxylic acid cycle activity in Staphylococcus aureus', Journal of Biological Chemistry, vol. 288, no. 50, pp. 36116-36128. https://doi.org/10.1074/jbc.M113.516302
Hartmann, Torsten ; Zhang, Bo ; Baronian, Grégory ; Schulthess, Bettina ; Homerova, Dagmar ; Grubmul̈ler, Stephanie ; Kutzner, Erika ; Gaupp, Rosmarie ; Bertram, Ralph ; Powers, Robert ; Eisenreich, Wolfgang ; Kormanec, Jan ; Herrmann, Mathias ; Molle, Virginie ; Somerville, Greg A ; Bischoff, Markus. / Catabolite control protein E (CcpE) is a LysR-type transcriptional regulator of tricarboxylic acid cycle activity in Staphylococcus aureus. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 50. pp. 36116-36128.
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AU - Hartmann, Torsten

AU - Zhang, Bo

AU - Baronian, Grégory

AU - Schulthess, Bettina

AU - Homerova, Dagmar

AU - Grubmul̈ler, Stephanie

AU - Kutzner, Erika

AU - Gaupp, Rosmarie

AU - Bertram, Ralph

AU - Powers, Robert

AU - Eisenreich, Wolfgang

AU - Kormanec, Jan

AU - Herrmann, Mathias

AU - Molle, Virginie

AU - Somerville, Greg A

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