Streptococcus pneumoniae Can Utilize Multiple Sources of Hyaluronic Acid for Growth

Marion, Carolyn; Stewart, Jason M.; Tazi, Mia; Burnaugh, Amanda M.; Linke, Caroline M.; Woodiga, Shireen A.; King, Samantha J.

doi:10.1128/iai.05756-11

Cited by 79 publications

(112 citation statements)

References 47 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…Recent studies have focused on the physiological functions and structures of UGLs and have revealed peculiar mechanisms of UGL catalysis using artificial substrates (15) and that UGL gene disruption leads to reduced upper respiratory tract colonization by Streptococcus pneumoniae (19). Specific inhibitors of UGL are therefore expected to provide anti-bacterial drugs with no side effects.…”

mentioning

confidence: 99%

Crystal Structure of a Bacterial Unsaturated Glucuronyl Hydrolase with Specificity for Heparin

Nakamichi

Mikami

Murata

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Bacterial unsaturated glucuronyl hydrolase (UGL) is essential for complete degradation of host glycosaminoglycans. Results: Crystal structure of Pedobacter heparinus UGL, Phep_2830 specific for heparin degradation, was determined. Conclusion: The pocket-like structure and lid loop of Phep_2830 are involved in heparin disaccharide recognition. Significance: This work contributes to understanding the bacterial degradation of host extracellular matrix components.

show abstract

mentioning

confidence: 99%

Crystal Structure of a Bacterial Unsaturated Glucuronyl Hydrolase with Specificity for Heparin

Nakamichi

Mikami

Murata

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The UGL genetic cluster of S. agalacitae is inducibly transcribed in the presence of hyaluronan (10). Recently, the disruption of the UGL genetic cluster in S. pneumoniae has been demonstrated to reduce the bacterial attachment to host cells and the ability to cause infectious diseases (11). These reports indicate the significance of the UGL genetic cluster in bacterial infections.…”

mentioning

confidence: 83%

“…Streptococci such as S. agalactiae, S. pneumoniae, and S. pyogenes include the UGL genetic cluster responsible for the depolymerization (by lyases (HysA and/or HepC) for hyaluronan and/or heparan sulfate), import (by the phosphotransferase system; PTS), and degradation (by UGL) of glycosaminoglycans in the bacterial genomes (10,11) (Fig. 2A).…”

Section: Metabolism Of Unsaturated Uronic Acids From Glycosaminoglycansmentioning

confidence: 99%

“…Two streptococci, S. pneumoniae and S. pyogenes, have been shown to grow on hyalruonan as the sole carbon source (11)(12)(13), but little knowledge about the bacterial assimilation mechanism of glycosaminoglycans has been accumulated. More recently, streptococcal UGL has been demonstrated to act on various unsaturated disaccharides, such as hyaluronan, chondroitin sulfate, heparin, and heparan sulfate, and to release unsaturated uronic acids and amino sugars (9,14).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Metabolic Fate of Unsaturated Glucuronic/Iduronic Acids from Glycosaminoglycans

Maruyama¹,

Oiki²,

Takase³

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Some streptococci target host extracellular matrix glycosaminoglycans for infection. Results: The streptococcal metabolic pathway of glycosaminoglycan-derived unsaturated uronates was identified. The crystal structures of its isomerase and dehydrogenase were determined. Conclusion: Streptococci include an assembled genetic cluster for depolymerization, import, degradation, and metabolism of glycosaminoglycans. Significance: This study contributes to understanding of the streptococcal degradation/metabolism mechanism of glycosaminoglycans.

show abstract

“…S. mutans transports GlcN and GlcNAc primarily via the EII Man permease, a fructose:mannose-type EII that is also the dominant transporter for glucose, mannose, and galactose (2)(3)(4). In fact, the PTS is the primary route for amino sugar uptake for most bacteria, providing cells with internalized GlcN-6-phosphate (GlcN-6-P) or GlcNAc-6-phosphate (GlcNAc-6-P) (5)(6)(7). To catabolize these phosphosugars, bacteria produce a GlcNAc-6-P deacetylase, encoded by nagA, that converts GlcNAc-6-P into GlcN-6-P. GlcN-6-P, generated either from GlcNAc by NagA or by PTS transport of GlcN, is deaminated by a GlcN-6-P deaminase (nagB) and concurrently isomerized to fructose-6-P (F-6-P), which can enter the Embden-Meyerhof-Parnas pathway (5).…”

mentioning

confidence: 99%

NagR Differentially Regulates the Expression of the glmS and nagAB Genes Required for Amino Sugar Metabolism by Streptococcus mutans

Zeng

Burne

2015

J Bacteriol

View full text Add to dashboard Cite

The ability of bacteria to metabolize glucosamine (GlcN) and N-acetyl-D-glucosamine (GlcNAc) is considered important for persistent colonization of the oral cavity. In the dental caries pathogen Streptococcus mutans, the NagR protein regulates the expression of glmS, which encodes a GlcN-6-P synthetase, and nagA (GlcNAc-6-P deacetylase) and nagB (GlcN-6-P deaminase), which are required for the catabolism of GlcNAc and GlcN. Two NagR-binding sites (dre) were identified in each of the promoter regions for nagB and glmS. Using promoter-reporter gene fusions, the role of each dre site was examined in the regulation of glmS and nagB promoter activities in cells grown with glucose, GlcNAc, or GlcN. A synergistic relationship between the two dre sites in the glmS promoter that required proper spacing was observed, but that was not the case for nagB. Binding of purified NagR to DNA fragments from both promoter regions, as well as to dre sites alone, was strongly influenced by particular sugar phosphates. Using a random mutagenesis approach that targeted the effector-binding domain of NagR, mutants that displayed aberrant regulation of both the glmS and nagAB genes were identified. Collectively, these findings provide evidence that NagR is essential for regulation of genes for both the synthesis and catabolism of GlcN and GlcNAc in S. mutans, and that NagR engages differently with the target promoter regions in response to specific metabolites interacting with the effector-binding domain of NagR. IMPORTANCEGlucosamine and N-acetylglucosamine are among the most abundant naturally occurring sugars on the planet, and they are catabolized by many bacterial species as sources of carbon and nitrogen. Representing a group called lactic acid bacteria (LAB), the human dental caries pathogen Streptococcus mutans is shown to differ from known paradigm organisms in that it possesses a GntR/HutC-type regulator, NagR, that is required for the regulation of both catabolism of GlcN and biosynthesis. Results reported here reveal a simple and elegant mechanism whereby NagR differentially regulates two opposing biological processes by surveying metabolic intermediates. This study provides insights that may contribute to the development of novel therapeutic tools to combat dental caries and other infectious diseases.A mino sugars, including glucosamine (GlcN) and N-acetyl-Dglucosamine (GlcNAc or NAG), are some of the most abundant carbohydrates on earth. Since amino sugars can serve as sources of carbon and nitrogen, many bacteria have the capacity to utilize them for energy production and growth. We recently showed that the human dental pathogen Streptococcus mutans internalizes GlcN and GlcNAc via the phosphoenolpyruvate (PEP): sugar phosphotransferase system (PTS), which consists of a general enzyme I (EI) and a phospho-carrier protein (HPr) that transfer the phosphoryl group from PEP to a variety of substratespecific EII enzymes responsible for the concurrent phosphorylation and internalization of their cognate sugars (1). S. mu...

show abstract

Streptococcus pneumoniae Can Utilize Multiple Sources of Hyaluronic Acid for Growth

Cited by 79 publications

References 47 publications

Crystal Structure of a Bacterial Unsaturated Glucuronyl Hydrolase with Specificity for Heparin

Crystal Structure of a Bacterial Unsaturated Glucuronyl Hydrolase with Specificity for Heparin

Metabolic Fate of Unsaturated Glucuronic/Iduronic Acids from Glycosaminoglycans

NagR Differentially Regulates the Expression of the glmS and nagAB Genes Required for Amino Sugar Metabolism by Streptococcus mutans

Contact Info

Product

Resources

About