Catabolite Repression

Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression.

Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kinase, also abrogated growth of JE2 in CDM, suggesting that ATP production from pyruvate-producing amino acids is also critical for growth. In addition, although a functional respiratory chain was absolutely required for growth, the oxygen consumption rate and intracellular ATP concentration were significantly lower during growth in CDM than during growth in glucose-containing media. Finally, transcriptional analyses demonstrated that expression levels of genes coding for the enzymes that synthesize glutamate from proline, arginine, and histidine are repressed by CcpA and carbon catabolite repression. These data show that pathways important for glutamate catabolism or ATP generation via Pta/AckA are important for growth in niches where glucose is not abundant, such as abscesses within skin and soft tissue infections.IMPORTANCES. aureus is a significant cause of both morbidity and mortality worldwide. This bacterium causes infections in a wide variety of organ systems, the most common being skin and soft tissue. Within a staphylococcal abscess, levels of glucose, a preferred carbon source, are limited due to the host immune response. Therefore, S. aureus must utilize other available carbon sources such as amino acids or peptides to proliferate. Our results show that glutamate and amino acids that serve as substrates for glutamate synthesis, particularly proline, function as major carbon sources during growth, whereas other amino acids that generate pyruvate are important for ATP synthesis via substrate-level phosphorylation in the Pta-AckA pathway. Our data support a model whereby certain amino acid catabolic pathways, and acquisition of those particular amino acids, are crucial for growth in niches where glucose is not abundant.

Carbon Catabolite Repression (CCR) has fascinated scientists and researchers around the globe for the past few decades. This important mechanism allows preferential utilization of an energy-efficient and readily available carbon source over relatively less easily accessible carbon sources. This mechanism helps microorganisms to obtain maximum amount of glucose in order to keep pace with their metabolism. Microorganisms assimilate glucose and highly favorable sugars before switching to less-favored sources of carbon such as organic acids and alcohols. In CCR of filamentous fungi, CreA acts as a transcription factor, which is regulated to some extent by ubiquitination. CreD-HulA ubiquitination ligase complex helps in CreA ubiquitination, while CreB-CreC deubiquitination (DUB) complex removes ubiquitin from CreA, which causes its activation. CCR of fungi also involves some very crucial elements such as Hexokinases, cAMP, Protein Kinase (PKA), Ras proteins, G protein-coupled receptor (GPCR), Adenylate cyclase, RcoA and SnfA. Thorough study of molecular mechanism of CCR is important for understanding growth, conidiation, virulence and survival of filamentous fungi. This review is a comprehensive revision of the regulation of CCR in filamentous fungi as well as an updated summary of key regulators, regulation of different CCR-dependent mechanisms and its impact on various physical characteristics of filamentous fungi.

Geobacillus kaustophilus HTA426 is a thermophilic Gram-positive bacterium that encodes the myo-inositol-inducible iol operons, the products of which form the myo-inositol catabolic pathway. Strain PS8 is a mutant of HTA426 that is defective in myo-inositol catabolism due to constitutive repression of the iol operons. Several spontaneous suppressor mutants of PS8, which restored growth on myo-inositol, were obtained. These suppressors had mutations that may affect the translation of crh. Inclusion of a plasmid-based copy of crh into the suppressor mutants concomitantly restored the repression of the iol operons. PS8 and its suppressor mutants shared a mutated allele of hprK(G268R) that may encode a defective HPr kinase/phosphorylase, which could lead to the accumulation of the phosphorylated form of Crh. Inclusion of a plasmid-based copy of the wild-type hprK gene into PS8 restored the induction of the iol operons. Conversely, inclusion of a plasmid-based copy of hprK(G268R) into HTA426 significantly repressed the iol operons. In HTA426, ribose, rather than glucose, repressed the iol operons. During the growth on ribose, the expression of ptsH, which encodes HPr, was kept at a low level, while that of crh was elevated. Deletion of hprK, ccpA (encoding global regulator CcpA) or the rbs operon (encoding the components for ribose catabolism) abolishes the ribose-induced repression of iol operons. These results suggest an atypical catabolite repression of the iol operons of G. kaustophilus HTA426, where HPrK phosphorylates Crh in the presence of ribose, and the phosphorylated form of Crh cooperates with CcpA to repress the transcription of the iol operons.