Mechanisms underlying CCR in firmicutes. Mechanisms underlying CCR in firmicutes. The uptake of glucose and other rapidly metabolizable PTS sugars (top left) leads to a net dephosphorylation of the PTS proteins. The center and bottom of the figure show that the high concentration of FBP present in cells growing on a rapidly metabolizable carbohydrate stimulates the HPr kinase activity of the bifunctional HprK/P and the formation of P-Ser-HPr. P-Ser-HPr interacts with CcpA, and the protein complex binds to the cre operator sites on the DNA. The promoter regions are indicated as −10 and −35. CCA occurs when the cre is located upstream from the promoter, while CCR requires a cre located within or downstream from the promoter. High concentrations of Pi present in resting cells favor the pyrophosphate-producing dephosphorylation of P-Ser-HPr by HprK/P. The top right part of the figure shows that P-Ser-HPr probably interacts with certain non-PTS carbohydrate transport systems, such as the maltose transporter from L. casei, and thereby inhibits their transport activity. Phosphorylation of LacS by P∼His-HPr stimulates the lactose/galactose exchange reaction (in S. thermophilus). In the presence of rapidly metabolizable PTS substrates, the low level of P∼His-HPr does not allow sufficient phosphorylation of GlpK, which leads to the inactivation of GlpK and to inducer exclusion. Pyr., pyruvate. Josef Deutscher et al. Microbiol. Mol. Biol. Rev. 2006; doi:10.1128/MMBR.00024-06