Transcriptional profiling of gene expression in response to glucose in Bacillus subtilis: regulation of the central metabolic pathways.

Chemoheterotrophic bacteria use a few central metabolic pathways for carbon catabolism and energy production as well as for the generation of the main precursors for anabolic reactions. All sources of carbon and energy are converted to intermediates of these central pathways and then further metabolized. While the regulation of genes encoding enzymes used to introduce specific substrates into the central metabolism has already been studied to some detail, much less is known about the regulation of the central metabolic pathways. In this study, we investigated the responses of the Bacillus subtilis transcriptome to the presence of glucose and analyzed the role of the pleiotropic transcriptional regulator CcpA in these responses. We found that CcpA directly represses genes involved in the utilization of secondary carbon sources. In contrast, induction by glucose seems to be mediated by a variety of different mechanisms. In the presence of glucose, the genes encoding glycolytic enzymes are induced. Moreover, the genes responsible for the production of acetate from pyruvate with a concomitant substrate-level phosphorylation are induced by glucose. In contrast, the genes required for the complete oxidation of the sugar (Krebs cycle, respiration) are repressed if excess glucose is available for the bacteria. In the absence of glucose, the genes of the Krebs cycle as well as gluconeogenic genes are derepressed. The genes encoding enzymes of the pentose phosphate pathway are expressed both in the presence and the absence of glucose, as suggested by the central role of this pathway in generating anabolic precursors.