J. Exp. Med., Volume 188, Number 11, December 7, 1998 2047-2056

Characterization of the galU Gene of Streptococcus pneumoniae Encoding a Uridine Diphosphoglucose Pyrophosphorylase: A Gene Essential for Capsular Polysaccharide Biosynthesis

By Marta Mollerach,^* Rubens López, and Ernesto García

From the ^* Departamento de Microbiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113 Buenos Aires, Argentina; and the  Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain

The galU gene of Streptococcus pneumoniae has been cloned and sequenced. Escherichia coli cells harboring the recombinant plasmid pMMG2 (galU) overproduced a protein that has been shown to correspond to a uridine 5'-triphosphate:glucose-1-phosphate uridylyltransferase (uridine diphosphoglucose [UDP-Glc] pyrophosphorylase) responsible for the synthesis of UDP-Glc, a key compound in the biosynthesis of polysaccharides. A gene very similar to the S. pneumoniae galU has been found in a partial nucleotide sequence of the Streptococcus pyogenes genome. Knockout galU mutants of type 1 pneumococci are unable to synthesize a detectable capsule. An identical result was found in type 3 S. pneumoniae cells in spite of the fact that these bacteria contain a type-specific gene (cap3C) that also encodes a UDP-Glc pyrophosphorylase. Since eukaryotic UDP-Glc pyrophosphorylases appear to be completely unrelated to their prokaryotic counterparts, we postulate that GalU may be an appropriate target for the search of new drugs to control the pathogenicity of bacteria like pneumococcus and S. pyogenes.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Aanensen, D. M., Mavroidi, A., Bentley, S. D., Reeves, P. R., Spratt, B. G. (2007). Predicted Functions and Linkage Specificities of the Products of the Streptococcus pneumoniae Capsular Biosynthetic Loci. J. Bacteriol. 189: 7856-7876 [Abstract] [Full Text]  
• Thoden, J. B., Holden, H. M. (2007). Active site geometry of glucose-1-phosphate uridylyltransferase. Protein Sci. 16: 1379-1388 [Abstract] [Full Text]  
• Thoden, J. B., Holden, H. M. (2007). The molecular architecture of glucose-1-phosphate uridylyltransferase. Protein Sci. 16: 432-440 [Abstract] [Full Text]  
• McEllistrem, M. C., Ransford, J. V., Khan, S. A. (2007). Characterization of In Vitro Biofilm-Associated Pneumococcal Phase Variants of a Clinically Relevant Serotype 3 Clone. J. Clin. Microbiol. 45: 97-101 [Abstract] [Full Text]  
• Kerr, A. R., Paterson, G. K., Riboldi-Tunnicliffe, A., Mitchell, T. J. (2005). Innate Immune Defense against Pneumococcal Pneumonia Requires Pulmonary Complement Component C3. Infect. Immun. 73: 4245-4252 [Abstract] [Full Text]  
• Barreto, M., Jedlicki, E., Holmes, D. S. (2005). Identification of a Gene Cluster for the Formation of Extracellular Polysaccharide Precursors in the Chemolithoautotroph Acidithiobacillus ferrooxidans. Appl. Environ. Microbiol. 71: 2902-2909 [Abstract] [Full Text]  
• Xu, D.-Q., Thompson, J., Cisar, J. O. (2003). Genetic Loci for Coaggregation Receptor Polysaccharide Biosynthesis in Streptococcus gordonii 38. J. Bacteriol. 185: 5419-5430 [Abstract] [Full Text]  
• Zhang, Y. L., Lau, Y. L., Arakawa, E., Leung, K. Y. (2003). Detection and genetic analysis of group II capsules in Aeromonas hydrophila. Microbiology 149: 1051-1060 [Abstract] [Full Text]  
• van Selm, S., Kolkman, M. A. B., van der Zeijst, B. A. M., Zwaagstra, K. A., Gaastra, W., van Putten, J. P. M. (2002). Organization and characterization of the capsule biosynthesis locus of Streptococcus pneumoniae serotype 9V. Microbiology 148: 1747-1755 [Abstract] [Full Text]  
• Levander, F., Svensson, M., Radstrom, P. (2002). Enhanced Exopolysaccharide Production by Metabolic Engineering of Streptococcus thermophilus. Appl. Environ. Microbiol. 68: 784-790 [Abstract] [Full Text]  
• Boels, I. C., Ramos, A., Kleerebezem, M., de Vos, W. M. (2001). Functional Analysis of the Lactococcus lactis galU and galE Genes and Their Impact on Sugar Nucleotide and Exopolysaccharide Biosynthesis. Appl. Environ. Microbiol. 67: 3033-3040 [Abstract] [Full Text]  
• Hardy, G. G., Magee, A. D., Ventura, C. L., Caimano, M. J., Yother, J. (2001). Essential Role for Cellular Phosphoglucomutase in Virulence of Type 3 Streptococcus pneumoniae. Infect. Immun. 69: 2309-2317 [Abstract] [Full Text]  
• Gilbert, C., Robinson, K., Le Page, R. W. F., Wells, J. M. (2000). Heterologous Expression of an Immunogenic Pneumococcal Type 3 Capsular Polysaccharide in Lactococcus lactis. Infect. Immun. 68: 3251-3260 [Abstract] [Full Text]  
• Hardy, G. G., Caimano, M. J., Yother, J. (2000). Capsule Biosynthesis and Basic Metabolism in Streptococcus pneumoniae Are Linked through the Cellular Phosphoglucomutase. J. Bacteriol. 182: 1854-1863 [Abstract] [Full Text]  
• Cartee, R. T., Forsee, W. T., Schutzbach, J. S., Yother, J. (2000). Mechanism of Type 3 Capsular Polysaccharide Synthesis in Streptococcus pneumoniae. J. Biol. Chem. 275: 3907-3914 [Abstract] [Full Text]  
• Muñoz, R., Mollerach, M., López, R., García, E. (1999). Characterization of the Type 8 Capsular Gene Cluster of Streptococcus pneumoniae. J. Bacteriol. 181: 6214-6219 [Abstract] [Full Text]  
• Llull, D., Munoz, R., Lopez, R., Garcia, E. (1999). A Single Gene (tts) Located outside the cap Locus Directs the Formation of Streptococcus pneumoniae Type 37 Capsular Polysaccharide: Type 37 Pneumococci Are Natural, Genetically Binary Strains. J. Exp. Med. 190: 241-252 [Abstract] [Full Text]  
• Llull, D., Garcia, E., Lopez, R. (2001). Tts, a Processive beta -Glucosyltransferase of Streptococcus pneumoniae, Directs the Synthesis of the Branched Type 37 Capsular Polysaccharide in Pneumococcus and Other Gram-positive Species. J. Biol. Chem. 276: 21053-21061 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS