Key Points
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Carbon catabolite repression (CCR) is a global regulatory mechanism that inhibits the expression and activities of functions for the use of secondary carbon sources when a preferred carbon source is present. This allows bacteria to selectively use substrates from a mixture of different carbon sources.
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CCR is achieved by completely different mechanisms in different bacteria. In enteric bacteria, such as Escherichia coli, CCR is exerted by the absence of transcription activation of secondary catabolic genes in the presence of a preferred substrate. By contrast, in Firmicutes, such as Bacillus subtilis, transcription repression is responsible for CCR.
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In other bacteria the mechanisms that underlie CCR are less defined. In pseudomonads, CCR involves translation repression by an RNA-binding protein. In many Actinobacteria, the glucose kinase triggers CCR by an as-yet-unknown mechanism.
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In addition to the global mechanisms that control CCR, various operon-specific mechanisms are superimposed. These include the inhibition of transporters and catabolic enzymes (inducer inclusion) and the inactivation of transcription factors (induction prevention).
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CCR has a key role in the expression of virulence-specific functions in many pathogenic bacteria. Mutants that are affected in the global CCR pathway are often non-virulent and are useful for live vaccination. In addition, the regulatory proteins that are involved in CCR are promising targets for future antimicrobial chemotherapy.
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CCR in E. coli has been mathematically modelled. Modelling revealed that 'minor factors', such as the amounts of the proteins that participate in CCR, are important. Moreover, the contributions of global and operon-specific mechanisms of CCR may differ for each gene system.
Abstract
Most bacteria can selectively use substrates from a mixture of different carbon sources. The presence of preferred carbon sources prevents the expression, and often also the activity, of catabolic systems that enable the use of secondary substrates. This regulation, called carbon catabolite repression (CCR), can be achieved by different regulatory mechanisms, including transcription activation and repression and control of translation by an RNA-binding protein, in different bacteria. Moreover, CCR regulates the expression of virulence factors in many pathogenic bacteria. In this Review, we discuss the most recent findings on the different mechanisms that have evolved to allow bacteria to use carbon sources in a hierarchical manner.
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Acknowledgements
The authors acknowledge J. Deutscher and the members of their laboratories for helpful discussions. Work in the authors' laboratories is supported by grants from the German Research Foundation, the Fonds der Chemischen Industrie and the Ministry of Education and Research (BMBF; SysMO grant number PtJ-BIUO/0313978D).
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Entrez Protein
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Glossary
- Diauxie
-
The sequential use of carbon sources in a mixture of two different substrates. A short lag phase in the growth curve before the use of the less-preferred substrate is typical for diauxic growth.
- Inducer exclusion
-
A mechanism of carbon catabolite repression by which the uptake or formation of the inducer of a catabolic operon is prevented in the presence of preferred carbon sources.
- Induction prevention
-
A mechanism of carbon catabolite repression by which the activity of PTS-regulation-domain-containing transcription factors is inhibited in the presence of preferred carbon sources.
- P-loop motif
-
A phosphate-binding loop in many ATP- and GTP-binding proteins. The P-loop is composed of a glycine-rich sequence that is followed by a lysine and a serine or a threonine.
- Lactose permease
-
The best-studied transport protein. Lactose permease concomitantly transports lactose and protons into the cell (symport). Uptake of these protons provides the energy for lactose transport and accumulation.
- PTS-regulatory domain
-
(PRD). A protein domain of ∼100 amino acids that is found in many transcription regulators and that is always present in duplicate in PRD-containing regulators. These domains can be phosphorylated by PTS components (either the sugar-specific EIIB or HPr) on conserved histidine residues and contribute to substrate induction and catabolite repression. The phosphorylation state of the PRDs determines the activity of the regulator.
- Antitermination
-
A regulatory mechanism by which the formation of a transcription terminator is prevented under inducing conditions. Many catabolic operons are controlled by protein-dependent antitermination systems that result in transcription elongation into the structural genes only in the presence of the substrate.
- Cellulolytic clostridia
-
Obligately anaerobic, spore-forming bacteria that can degrade cellulose. Cellulolytic clostridia form an extracellular protein complex, called the cellulosome, that makes the cellulose fibres accessible to the cellulases that hydrolyse the cellulose.
- Trigger enzyme
-
An enzyme that is involved in the control of gene expression in response to gene-activity states. These enzymes can exert their regulatory functions by acting as direct transcription factors (binding to DNA or RNA) or by controlling the activity of other transcription factors (by covalent modification or regulatory protein–protein interactions).
- Pathogenicity island
-
A DNA region with clusters of genes that are involved in virulence functions. Pathogenicity islands are mobile genetic elements that are typically flanked by repeat structures and mobility genes that are required for horizontal gene transfer.
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Görke, B., Stülke, J. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6, 613–624 (2008). https://doi.org/10.1038/nrmicro1932
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DOI: https://doi.org/10.1038/nrmicro1932
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