Carbon catabolite repression in bacteria: many ways to make the most out of nutrients

Abstract

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. 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. 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. 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). 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. 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.