CcpA-Mediated Catabolite Regulation in Gram-Positive Bacteria

Catabolite control protein A (CcpA) is the principal regulator that orchestrates carbon catabolite repression and activation in Gram-positive bacteria, ensuring preferential utilisation of high-energy sugars such as glucose. Activated by binding to the phosphorylated coregulatory protein HPr-Ser46-P and the metabolic effector fructose-1,6-bisphosphate, CcpA recognises specific DNA motifs known as catabolite response elements (cre) within promoter regions. Through this interaction, CcpA dynamically modulates transcription of operons involved in carbohydrate uptake, glycolysis, gluconeogenesis and secondary metabolism. The resultant regulatory network aligns gene expression with environmental nutrient availability, optimises growth yield and influences traits such as virulence factor production, biofilm formation and stress resilience. Recent structural and genomic studies have uncovered significant plasticity in cre sequences, revealing both canonical and variable architectures that expand the CcpA regulon across diverse taxa. This global regulatory system underpins biotechnological applications, including industrial fermentation and antimicrobial target discovery, by harnessing metabolic fluxes and controlling pathogenicity determinants.

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CcpA-Mediated Catabolite Regulation in Gram-Positive Bacteria publication trend

The graph below shows the total number of articles in ccpa-mediated catabolite regulation in gram-positive bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

CcpA: Catabolite control protein A, a transcriptional regulator coordinating carbon source utilisation in Gram-positive bacteria.

Carbon catabolite repression (CCR): A regulatory mechanism by which the presence of a preferred carbon source represses genes for alternative substrate metabolism.

Catabolite response element (cre): A DNA sequence motif recognised by the CcpA–HPr-Ser46-P complex to activate or repress target promoters.

HPr-Ser46-P: Phosphorylated histidine-containing protein that serves as a coregulatory ligand for CcpA, integrating signals from the phosphotransferase system.

Phosphotransferase system (PTS): A multicomponent transport and signalling cascade that couples sugar uptake to protein phosphorylation, thereby linking metabolism to gene regulation.

References

1. Novel motif associated with carbon catabolite repression in two major Gram-positive pathogen virulence regulatory proteins. Microbiology Spectrum (2024).
2. Transcriptional control of carbohydrate catabolism by the CcpA protein in the ruminal bacterium Streptococcus bovis. Applied and Environmental Microbiology (2023).
3. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria. mBio (2017).