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; Homerová, Dagmar; Grubmüller, Stephanie; Kutzner, Erika; Gaupp, R.; Bertram, Ralph; Powers, Robert; Eisenreich, Wolfgang; Kormanec, Ján; Herrmann, Mathias; Molle, Virginie; Somerville, Greg A.; Bischoff, Markus

doi:10.1074/jbc.m113.516302

Cited by 44 publications

(39 citation statements)

References 57 publications

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“…A recent study showed that citrate does not affect CcpE binding to DNA (23). However, the amino acid sequence and DNA-binding sites of CcpE (Fig.…”

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 88%

“…Given that the deletion of ccpE causes reduced expression of citB (the gene encoding aconitase, the second enzyme of the TCA cycle) (23) and that disruption of TCA-cycle genes causes enhanced staphyloxanthin production (24), we next sought to determine if the constitutive expression of citB could suppress the effect of ccpE deletion on the production of staphyloxanthin.…”

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 99%

“…A recent study has shown that CcpE binds to the promoter of citB and activates its expression (23). To delineate further the function of CcpE on the regulation of citB, we searched for potential CcpEbinding sites in the promoter region of citB using a dye-based DNase I footprinting analysis.…”

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 99%

“…In addition to the increased siderophore production, the deletion of ccpE also caused a decrease in pH in the culture medium when bacteria reached the postexponential growth phase (23). Because both siderophore and acidic pH promote the release of iron from transferrin, we measured the capacity of the culture supernatants to release iron from transferrin.…”

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 99%

“…Here we show that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, binds to and activates catabolite control protein E (CcpE) (23). We found that CcpE acts as a master regulator for the expression of virulence factors, central metabolism, iron acquisition, and bacterial virulence of S. aureus.…”

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confidence: 96%

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Metabolic sensor governing bacterial virulence in Staphylococcus aureus

Ding¹,

Liu

Chen³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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An effective metabolism is essential to all living organisms, including the important human pathogen Staphylococcus aureus. To establish successful infection, S. aureus must scavenge nutrients and coordinate its metabolism for proliferation. Meanwhile, it also must produce an array of virulence factors to interfere with host defenses. However, the ways in which S. aureus ties its metabolic state to its virulence regulation remain largely unknown. Here we show that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, binds to and activates the catabolite control protein E (CcpE) of S. aureus. Using structural and site-directed mutagenesis studies, we demonstrate that two arginine residues (Arg145 and Arg256) within the putative inducer-binding cavity of CcpE are important for its allosteric activation by citrate. Microarray analysis reveals that CcpE tunes the expression of 126 genes that comprise about 4.7% of the S. aureus genome. Intriguingly, although CcpE is a major positive regulator of the TCA-cycle activity, its regulon consists predominantly of genes involved in the pathogenesis of S. aureus. Moreover, inactivation of CcpE results in increased staphyloxanthin production, improved ability to acquire iron, increased resistance to whole-blood-mediated killing, and enhanced bacterial virulence in a mouse model of systemic infection. This study reveals CcpE as an important metabolic sensor that allows S. aureus to sense and adjust its metabolic state and subsequently to coordinate the expression of virulence factors and bacterial virulence.Staphylococcus aureus | metabolism | iron acquisition | virulence gene expression | bacterial virulence

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“…A recent study showed that citrate does not affect CcpE binding to DNA (23). However, the amino acid sequence and DNA-binding sites of CcpE (Fig.…”

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 88%

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 99%

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 99%

Section: Deletion Of Ccpe Led To Enhanced Staphyloxanthin Productionmentioning

confidence: 99%

mentioning

confidence: 96%

See 3 more Smart Citations

Metabolic sensor governing bacterial virulence in Staphylococcus aureus

Ding¹,

Liu

Chen³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Comparative genomics and secretome profiling of Enterobacter cloacae SBP-8

Kumari,

Sharma,

et al. 2024

Biologia

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Phosphorylation-mediated regulation of the Staphylococcus aureus secreted tyrosine phosphatase PtpA

Brelle¹,

Baronian²,

Huc-Brandt³

et al. 2016

Biochemical and Biophysical Research Communications

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Catabolite Control Protein E (CcpE) Is a LysR-type Transcriptional Regulator of Tricarboxylic Acid Cycle Activity in Staphylococcus aureus

Cited by 44 publications

References 57 publications

Metabolic sensor governing bacterial virulence in Staphylococcus aureus

Metabolic sensor governing bacterial virulence in Staphylococcus aureus

Comparative genomics and secretome profiling of Enterobacter cloacae SBP-8

Phosphorylation-mediated regulation of the Staphylococcus aureus secreted tyrosine phosphatase PtpA

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