Molecular Characterization of CcpA and Involvement of This Protein in Transcriptional Regulation of Lactate Dehydrogenase and Pyruvate Formate-Lyase in the Ruminal Bacterium
            <i>Streptococcus bovis</i>

Asanuma, Narito; Yoshii, Toshitaka; Hino, Tsuneo

doi:10.1128/aem.70.9.5244-5251.2004

Cited by 34 publications

(37 citation statements)

References 43 publications

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“…In anaerobic conditions and in the presence of slowly fermentable sugars, PFL is responsible for the shift from homolactic to mixed-acid fermentation in L. lactis (3,25). In S. bovis, it was shown that pfl expression is also dependent on the nature of the fermentable carbon source via a CcpA-dependent mechanism (4,9). In the strain LMG18311, a catabolite-responsive element (cre box) was detected upstream of pfl (sequence TGTAAGCGGTTACT, at Ϫ92 bp upstream of the putative ATG start codon), suggesting that the nature of the carbon source would also modulate pfl expression in S. thermophilus.…”

Section: Discussionmentioning

confidence: 99%

Proteome Analysis of Streptococcus thermophilus Grown in Milk Reveals Pyruvate Formate-Lyase as the Major Upregulated Protein

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Mistou

et al. 2005

Appl Environ Microbiol

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We investigated the adaptation to milk of Streptococcus thermophilus LMG18311 using a proteomic approach. Two-dimensional electrophoresis of cytosolic proteins were performed after growth in M17 medium or in milk. A major modification of the proteome concerned proteins involved in the supply of amino acids, like the peptidase PepX, and several enzymes involved in amino acid biosynthesis. In parallel, we observed the upregulation of the synthesis of seven enzymes directly involved in the synthesis of purines, as well as formyl-tetrahydrofolate (THF) synthetase and serine hydroxy-methyl transferase, two enzymes responsible for the synthesis of compounds (THF and glycine, respectively) feeding the purine biosynthetic pathway. The analysis also revealed a massive increase in the synthesis of pyruvate formate-lyase (PFL), the enzyme which converts pyruvate into acetyl coenzyme A and formate. PFL has been essentially studied for its role in mixed-acid product formation in lactic acid bacteria during anaerobic fermentation. However, formate is an important methyl group donor for anabolic pathway through the formation of folate derivates. We hypothesized that PFL was involved in purine biosynthesis during growth in milk. We showed that PFL expression was regulated at the transcriptional level and that pfl transcription occurred during the exponential growth phase in milk. The complementation of milk with formate or purine bases was shown to reduce pfl expression, to suppress PFL synthesis, and to stimulate growth of S. thermophilus. These results show a novel regulatory mechanism controlling the synthesis of PFL and suggest an unrecognized physiological role for PFL as a formate supplier for anabolic purposes.The thermophilic bacteria Streptococcus thermophilus is one of the most widely used lactic acid bacteria (LAB) in the dairy fermentation industry for yoghurt and cheese production. In the industrial implementation of S. thermophilus, fast-growing capacity is crucial to enable rapid and intense acidification of milk. Identification of functions activated during growth in milk should help to understand the molecular adaptation of this bacterium to milk and provide the basis for targeted strain selection.In contrast with other LAB, the only environment from which S. thermophilus has been isolated is milk (38). In line with this restricted ecological niche, lactose, not glucose, is the preferred carbon source for S. thermophilus (31). The capacity to ferment lactose, the main sugar of milk, into lactic acid is essential for growth in milk and depends on a non-phosphotransferase system lactose permease (LacS) and a beta-galactosidase (LacZ) (40). Concerning the capacity of S. thermophilus to fulfill its amino acid needs during growth in milk, the species displays only a few amino acid auxotrophies compared to the model LAB, L. lactis (29,33). The growth of Lactococcus lactis in milk depends largely on the activity of a cell-wallbound proteinase (PrtP) that is responsible for casein hydrolysis, the main source of amino a...

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Section: Discussionmentioning

confidence: 99%

Proteome Analysis of Streptococcus thermophilus Grown in Milk Reveals Pyruvate Formate-Lyase as the Major Upregulated Protein

Derzelle

Bolotin

Mistou

et al. 2005

Appl Environ Microbiol

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“…CcpA has also been identified to function in the regulation of catabolic operons and catabolite repression in many Streptococcus spp. (1,17,59,77). CcpA has also shown to be required for biofilm formation in Streptococcus mutans (80).…”

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“…This interaction increases the affinity of CcpA for the cre. Binding of this dimeric complex typically causes repression of promoters, facilitating CCR (1,13,14). CcpA residues involved in binding of Pϳ Ser-HPr (38) and those involved in binding of cre (37) have been characterized, and the crystal structure of the CcpA-Pϳ Ser-HPr complex has been recently solved (63).…”

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Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

2005

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We characterized the role of catabolite control protein A (ccpA) in the physiology and virulence of Streptococcus pneumoniae. S. pneumoniae has a large percentage of its genome devoted to sugar uptake and metabolism, and therefore, regulation of these processes is likely to be crucial for fitness in the nasopharynx and may play a role during invasive disease. In many bacteria, carbon catabolite repression (CCR) is central to such regulation, influencing hierarchical sugar utilization and growth rates. CcpA is the major transcriptional regulator in CCR in several gram-positive bacteria. We show that CcpA functions in CCR of lactose-inducible ␤-galactosidase activity in S. pneumoniae. CCR of maltose-inducible ␣-glucosidase, raffinose-inducible ␣-galactosidase, and cellobiose-inducible ␤-glucosidase is unaffected in the ccpA strain, suggesting that other regulators, possibly redundant with CcpA, control these systems. The ccpA strain is severely attenuated for nasopharyngeal colonization and lung infection in the mouse, establishing its role in fitness on these mucosal surfaces. Comparison of the cell wall fraction of the ccpA and wild-type strains shows that CcpA regulates many proteins in this compartment that are involved in central and intermediary metabolism, a subset of which are required for survival and multiplication in vivo. Both in vitro and in vivo defects were complemented by providing ccpA in trans. Our results demonstrate that CcpA, though not a global regulator of CCR in S. pneumoniae, is required for colonization of the nasopharynx and survival and multiplication in the lung.Carbon metabolism and its regulation are central to prokaryotic life. Sugars serve as the most facile source of carbon and energy, both of which are needed to replenish essential nucleotide cofactors and other metabolites in the cell. When faced with a wide variety of carbon and energy sources, a bacterium has to make metabolic decisions, opting for preferential use of one source over another in order to maintain optimal growth (70, 74).

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“…When present, the pneumococcus modifies gene expression to ensure the prioritized usage of these sugars through a process called carbon catabolite repression (CCR). Pertinent to this article, glucose-mediated CCR results in the conversion of pyruvate to lactate, using the enzyme lactate dehydrogenase (24). Whereas in the absence of glucose and growth in galactose, pyruvate is converted to acetyl phosphate using the enzyme pyruvate oxidase (Fig.…”

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Neuraminidase A-Exposed Galactose Promotes Streptococcus pneumoniae Biofilm Formation during Colonization

et al. 2016

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f Streptococcus pneumoniae is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose is absent from the nasopharynx, whereas galactose is abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells, thereby increasing its availability during colonization. We observed that S. pneumoniae mutants deficient in NanA and ␤-galactosidase A (BgaA) failed to form biofilms in vivo despite normal biofilm-forming abilities in vitro. Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose, and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network in which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate under non-CCR-inducing growth conditions, was unable to form biofilms. Subsequent comparative transcriptome sequencing (RNA-seq) analyses of planktonic and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently upregulated during diverse biofilm growth conditions. We conclude that carbon availability in the nasopharynx impacts pneumococcal biofilm formation in vivo. Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role.

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Molecular Characterization of CcpA and Involvement of This Protein in Transcriptional Regulation of Lactate Dehydrogenase and Pyruvate Formate-Lyase in the Ruminal Bacterium Streptococcus bovis

Cited by 34 publications

References 43 publications

Proteome Analysis of Streptococcus thermophilus Grown in Milk Reveals Pyruvate Formate-Lyase as the Major Upregulated Protein

Proteome Analysis of Streptococcus thermophilus Grown in Milk Reveals Pyruvate Formate-Lyase as the Major Upregulated Protein

Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

Neuraminidase A-Exposed Galactose Promotes Streptococcus pneumoniae Biofilm Formation during Colonization

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