Global control of sugar metabolism: a gram-positive solution.

Bacteria utilise carbon sources in a strictly controlled hierarchical manner for which they have developed global control mechanisms that govern and coordinate carbon source-specific regulation. This is achieved via carbon catabolite repression (CCR), which is the result of global transcriptional control and inducer exclusion. A common mechanism for transcriptional control has evolved within the group of low-GC Gram-positive bacteria, including lactic acid bacteria. The seryl-phosphorylated form of the phosphotransferase HPr (HPr-ser-P) mediates CCR in concert with the pleiotropic regulator CcpA (catabolite control protein) by repressing or activating catabolite-controlled genes. HPr-ser-P can concomitantly trigger inducer exclusion by inhibition of carbohydrate-specific permeases. Histidyl-phosphorylated HPr (HPr-his P) is required for the transport of many carbon sources by the phosphotransferase system (PTS). In addition, HPr-his P controls carbohydrate-specific regulators and catabolic enzymes by phosphorylation. Thus, the ratio of HPr-his P/HPr-ser-P determines utilisation of a particular carbon source. This ratio is mainly adjusted by the bifunctional HPr kinase/phosphatase (HPrK/P), which itself is controlled by the metabolic state of the cell. As a result, the information about the metabolic state of the cell is combined with signals scoring the availability of carbon sources to fine-tune the expression of catabolic genes with the goal to optimise growth rate in any given mixture of nutrients. This review summarises the current understanding of carbon catabolite regulation in low-GC Gram-positive bacteria with special emphasis on lactic acid bacteria.