Protein kinase-dependent HPr/CcpA interaction links glycolytic activity to carbon catabolite repression in Gram-positive bacteria

1995 ◽  
Vol 15 (6) ◽  
pp. 1049-1053 ◽  
Author(s):  
Josef Deutscher ◽  
Elke Küster ◽  
Uta Bergstedt ◽  
Véronique Charrier ◽  
Wolfgang Hillen
Keyword(s):  
Protein Kinase ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Glycolytic Activity

scholarly journals CcpA-Dependent Carbon Catabolite Repression in Bacteria

2003 ◽  
Vol 67 (4) ◽  
pp. 475-490 ◽  
Author(s):  
Jessica B. Warner ◽  
Juke S. Lolkema
Keyword(s):  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Serine Phosphorylation ◽  
Regulation System ◽  
Sequence Motif ◽  
Phosphotransferase System ◽  
Gram Positive ◽  
The Public ◽  
Gram Positive Bacteria ◽  
Close Phylogenetic Relationship

SUMMARY Carbon catabolite repression (CCR) by transcriptional regulators follows different mechanisms in gram-positive and gram-negative bacteria. In gram-positive bacteria, CcpA-dependent CCR is mediated by phosphorylation of the phosphoenolpyruvate:sugar phosphotransferase system intermediate HPr at a serine residue at the expense of ATP. The reaction is catalyzed by HPr kinase, which is activated by glycolytic intermediates. In this review, the distribution of CcpA-dependent CCR among bacteria is investigated by searching the public databases for homologues of HPr kinase and HPr-like proteins throughout the bacterial kingdom and by analyzing their properties. Homologues of HPr kinase are commonly observed in the phylum Firmicutes but are also found in the phyla Proteobacteria, Fusobacteria, Spirochaetes, and Chlorobi, suggesting that CcpA-dependent CCR is not restricted to gram-positive bacteria. In the α and β subdivisions of the Proteobacteria, the presence of HPr kinase appears to be common, while in the γ subdivision it is more of an exception. The genes coding for the HPr kinase homologues of the Proteobacteria are in a gene cluster together with an HPr-like protein, termed XPr, suggesting a functional relationship. Moreover, the XPr proteins contain the serine phosphorylation sequence motif. Remarkably, the analysis suggests a possible relation between CcpA-dependent gene regulation and the nitrogen regulation system (Ntr) found in the γ subdivision of the Proteobacteria. The relation is suggested by the clustering of CCR and Ntr components on the genome of members of the Proteobacteria and by the close phylogenetic relationship between XPr and NPr, the HPr-like protein in the Ntr system. In bacteria in the phylum Proteobacteria that contain HPr kinase and XPr, the latter may be at the center of a complex regulatory network involving both CCR and the Ntr system.

PTS 50: Past, Present and Future, or Diauxie Revisited

2015 ◽  
Vol 25 (2-3) ◽  
pp. 79-93 ◽  
Author(s):  
Joseph W. Lengeler
Keyword(s):  
Catabolite Repression ◽  
Biological Significance ◽  
Cellular Growth ◽  
Gram Positive ◽  
Gram Negative ◽  
Inducer Exclusion ◽  
Gram Positive Bacteria ◽  
Cellular Control

<b><i>Past:</i></b> The title ‘PTS 50 or The PTS after 50 years' relies on the first description in 1964 of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) by Kundig, Gosh and Roseman [Proc Natl Acad Sci USA 1964;52:1067-1074]. The system comprised proteins named Enzyme I, HPr and Enzymes II, as part of a novel PTS for carbohydrates in Gram-negative and Gram-positive bacteria, whose ‘biological significance remained unclear'. In contrast, studies which would eventually lead to the discovery of the central role of the PTS in bacterial metabolism had been published since before 1942. They are primarily linked to names like Epps and Gale, J. Monod, Cohn and Horibata, and B. Magasanik, and to phenomena like ‘glucose effects', ‘diauxie', ‘catabolite repression' and carbohydrate transport. <b><i>Present:</i></b> The pioneering work from Roseman's group initiated a flood of publications. The extraordinary progress from 1964 to this day in the qualitative and in vitro description of the genes and enzymes of the PTS, and of its multiple roles in global cellular control through ‘inducer exclusion', gene induction and ‘catabolite repression', in cellular growth, in cell differentiation and in chemotaxis, as well as the differences of its functions between Gram-positive and Gram-negative bacteria, was one theme of the meeting and will not be treated in detail here. <b><i>Future:</i></b> At the 1988 Paris meeting entitled ‘The PTS after 25 years', Saul Roseman predicted that ‘we must describe these interactions [of the PTS components] in a quantitative way [under] in vivo conditions'. I will present some results obtained by our group during recent years on the old phenomenon of diauxie by means of very fast and quantitative tests, measured in vivo, and obtained from cultures of isogenic mutant strains growing under chemostat conditions. The results begin to hint at the problems relating to future PTS research, but also to the ‘true science' of Roseman.

scholarly journals CcpA Mediates Proline Auxotrophy and Is Required for Staphylococcus aureus Pathogenesis

2010 ◽  
Vol 192 (15) ◽  
pp. 3883-3892 ◽  
Author(s):  
Chunling Li ◽  
Fei Sun ◽  
Hoonsik Cho ◽  
Vamshi Yelavarthi ◽  
Changmo Sohn ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Selective Pressure ◽  
Missense Mutations ◽  
Ornithine Aminotransferase ◽  
Gram Positive Bacteria ◽  
The Third ◽  
Transposon Insertion ◽  
Ornithine Cyclodeaminase

ABSTRACT Human clinical isolates of Staphylococcus aureus, for example, strains Newman and N315, cannot grow in the absence of proline, albeit their sequenced genomes harbor genes for two redundant proline synthesis pathways. We show here that under selective pressure, S. aureus Newman generates proline-prototrophic variants at a frequency of 3 × 10−6, introducing frameshift and missense mutations in ccpA or IS1811 insertions in ptsH, two regulatory genes that carry out carbon catabolite repression (CCR) in staphylococci and other Gram-positive bacteria. S. aureus Newman variants with mutations in rocF (arginase), rocD (ornithine aminotransferase), and proC (Δ1-pyrroline 5-carboxylate [P5C] reductase) are unable to generate proline-prototrophic variants, whereas a variant with a mutation in ocd (ornithine cyclodeaminase) is unaffected. Transposon insertion in ccpA also restored proline prototrophy. CcpA was shown to repress transcription of rocF and rocD, encoding the first two enzymes, but not of proC, encoding the third and final enzyme in the P5C reductase pathway. CcpA bound to the upstream regions of rocF and rocD but not to that of proC. CcpA's binding to the upstream regions was greatly enhanced by phosphorylated HPr. The CCR-mediated proline auxotrophy was lifted when nonpreferred carbohydrates were used as the sole carbon source. The ccpA mutant displayed reduced staphylococcal load and replication in a murine model of staphylococcal abscess formation, indicating that carbon catabolite repression presents an important pathogenesis strategy of S. aureus infections.

CreA-independent carbon catabolite repression of cellulase genes by trimeric G-protein and protein kinase A in Aspergillus nidulans

2019 ◽  
Vol 65 (4) ◽  
pp. 941-952 ◽  
Author(s):  
Emi Kunitake ◽  
Yi Li ◽  
Ryota Uchida ◽  
Takehiro Nohara ◽  
Keisuke Asano ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Aspergillus Nidulans ◽  
G Protein ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Kinase A

scholarly journals A novel protein kinase that controls carbon catabolite repression in bacteria

1998 ◽  
Vol 27 (6) ◽  
pp. 1157-1169 ◽  
Author(s):  
Jonathan Reizer ◽  
Christian Hoischen ◽  
Friedrich Titgemeyer ◽  
Carlo Rivolta ◽  
Ralf Rabus ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Novel Protein

scholarly journals MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling

2021 ◽  
Author(s):  
Sabrina Wamp ◽  
Patricia Rothe ◽  
Gudrun Holland ◽  
Sven Halbedel
Keyword(s):  
Cell Wall ◽  
Listeria Monocytogenes ◽  
Protein Kinase ◽  
Bacterial Cell ◽  
Bacterial Cell Wall ◽  
Escape Mutation ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Main Component ◽  
Biosynthesis Regulation

AbstractGram-positive bacteria are protected by a thick mesh of peptidoglycan (PG) completely engulfing their cells. This PG network is the main component of the bacterial cell wall, it provides rigidity and acts as foundation for the attachment of other surface molecules. Biosynthesis of PG consumes a high amount of cellular resources and therefore requires careful adjustments to environmental conditions.An important switch in the control of PG biosynthesis of Listeria monocytogenes, a Gram-positive pathogen with a high infection fatality rate, is the serine/threonine protein kinase PrkA. A key substrate of this kinase is the small cytosolic protein ReoM. We have shown previously that ReoM phosphorylation regulates PG formation through control of MurA stability. MurA catalyzes the first step in PG biosynthesis and the current model suggests that phosphorylated ReoM prevents MurA degradation by the ClpCP protease. In contrast, conditions leading to ReoM dephosphorylation stimulate MurA degradation. How ReoM controls degradation of MurA and potential other substrates is not understood. Also, the individual contribution of the ∼20 other known PrkA targets to PG biosynthesis regulation is unknown.We here present murA mutants which escape proteolytic degradation. The release of MurA from ClpCP-dependent proteolysis was able to constitutively activate PG biosynthesis and further enhances the intrinsic cephalosporin resistance of L. monocytogenes. This activation required the RodA3/PBP B3 transglycosylase/transpeptidase pair as additional effectors of the PrkA signaling route. One murA escape mutation not only fully rescued an otherwise non-viable prkA mutant during growth in batch culture and inside macrophages but also overcompensated cephalosporin hypersensitivity. Our data collectively indicate that the main purpose of PrkA-mediated signaling in L. monocytogenes is control of MurA stability during extra- and intracellular growth. These findings have important implications for the understanding of PG biosynthesis regulation and β-lactam resistance of L. monocytogenes and related Gram-positive bacteria.Author SummaryPeptidoglycan (PG) is the main component of the bacterial cell wall and many of the PG synthesizing enzymes are antibiotic targets. We previously have discovered a new signaling route controlling PG production in the human pathogen Listeria monocytogenes. This route also determines the intrinsic resistance of L. monocytogenes against cephalosporins, a group of β-lactam antibiotics. Signaling involves PrkA, a membrane-embedded protein kinase, that is activated during cell wall stress to phosphorylate its target ReoM. Depending on its phosphorylation, ReoM activates or inactivates PG production by controlling the proteolytic stability of MurA, which catalyzes the first step in PG biosynthesis. MurA degradation depends on the ClpCP protease and we here have isolated murA mutations that escape this degradation. Using these mutants, we could show that regulation of PG biosynthesis through control of MurA stability is the primary purpose of PrkA-mediated signaling in L. monocytogenes. Further experiments identified the transglycosylase RodA and the transpeptidase PBP B3 as additional effectors of PrkA signaling. Our results suggest that both proteins act together to translate the signals received by PrkA into intensification of PG biosynthesis. These findings shed new light on the regulation of PG biosynthesis in Gram-positive bacteria with intrinsic β-lactam resistance.

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