This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Beverley, S. M.
Right arrow Articles by McNeil, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beverley, S. M.
Right arrow Articles by McNeil, M. R.

 Previous Article  |  Next Article 

Eukaryotic Cell, June 2005, p. 1147-1154, Vol. 4, No. 6
1535-9778/05/$08.00+0     doi:10.1128/EC.4.6.1147-1154.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Eukaryotic UDP-Galactopyranose Mutase (GLF Gene) in Microbial and Metazoal Pathogens{dagger}

Stephen M. Beverley,1* Katherine L. Owens,1 Melissa Showalter,1 Cara L. Griffith,1 Tamara L. Doering,1 Victoria C. Jones,2 and Michael R. McNeil2

Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110,1 Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 805232

Received 19 February 2005/ Accepted 29 March 2005

Galactofuranose (Galf) is a novel sugar absent in mammals but present in a variety of pathogenic microbes, often within glycoconjugates that play critical roles in cell surface formation and the infectious cycle. In prokaryotes, Galf is synthesized as the nucleotide sugar UDP-Galf by UDP-galactopyranose mutase (UGM) (gene GLF). Here we used a combinatorial bioinformatics screen to identify a family of candidate eukaryotic GLFs that had previously escaped detection. GLFs from three pathogens, two protozoa (Leishmania major and Trypanosoma cruzi) and one fungus (Cryptococcus neoformans), had UGM activity when expressed in Escherichia coli and assayed in vivo and/or in vitro. Eukaryotic GLFs are closely related to each other but distantly related to prokaryotic GLFs, showing limited conservation of core residues around the substrate-binding site and flavin adenine dinucleotide binding domain. Several eukaryotes not previously investigated for Galf synthesis also showed strong GLF homologs with conservation of key residues. These included other fungi, the alga Chlamydomonas and the algal phleovirus Feldmannia irregularis, parasitic nematodes (Brugia, Onchocerca, and Strongyloides) and Caenorhabditis elegans, and the urochordates Halocynthia and Cionia. The C. elegans open reading frame was shown to encode UGM activity. The GLF phylogenetic distribution suggests that Galf synthesis may occur more broadly in eukaryotes than previously supposed. Overall, GLF/Galf synthesis in eukaryotes appears to occur with a disjunct distribution and often in pathogenic species, similar to what is seen in prokaryotes. Thus, UGM inhibition may provide an attractive drug target in those eukaryotes where Galf plays critical roles in cellular viability and virulence.

* Corresponding author. Mailing address: Department of Molecular Microbiology, Washington University Medical School, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 747-2630. Fax: (314) 747-2634. E-mail: beverley{at}borcim.wustl.edu.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, June 2005, p. 1147-1154, Vol. 4, No. 6
1535-9778/05/$08.00+0     doi:10.1128/EC.4.6.1147-1154.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Engel, J., Schmalhorst, P. S., Dork-Bousset, T., Ferrieres, V., Routier, F. H. (2009). A Single UDP-galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus fumigatus. J. Biol. Chem. 284: 33859-33868 [Abstract] [Full Text]  
  • Grijpstra, J., Gerwig, G. J., Wosten, H., Kamerling, J. P., de Cock, H. (2009). Production of Extracellular Polysaccharides by CAP Mutants of Cryptococcus neoformans. Eukaryot Cell 8: 1165-1173 [Abstract] [Full Text]  
  • Madeira da Silva, L., Owens, K. L., Murta, S. M. F., Beverley, S. M. (2009). Regulated expression of the Leishmania major surface virulence factor lipophosphoglycan using conditionally destabilized fusion proteins. Proc. Natl. Acad. Sci. USA 106: 7583-7588 [Abstract] [Full Text]  
  • Schmalhorst, P. S., Krappmann, S., Vervecken, W., Rohde, M., Muller, M., Braus, G. H., Contreras, R., Braun, A., Bakker, H., Routier, F. H. (2008). Contribution of Galactofuranose to the Virulence of the Opportunistic Pathogen Aspergillus fumigatus. Eukaryot Cell 7: 1268-1277 [Abstract] [Full Text]  
  • Damveld, R. A., Franken, A., Arentshorst, M., Punt, P. J., Klis, F. M., van den Hondel, C. A. M. J. J., Ram, A. F. J. (2008). A Novel Screening Method for Cell Wall Mutants in Aspergillus niger Identifies UDP-Galactopyranose Mutase as an Important Protein in Fungal Cell Wall Biosynthesis. Genetics 178: 873-881 [Abstract] [Full Text]  
  • Turnock, D. C., Ferguson, M. A. J. (2007). Sugar Nucleotide Pools of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major. Eukaryot Cell 6: 1450-1463 [Abstract] [Full Text]  
  • Capul, A. A., Barron, T., Dobson, D. E., Turco, S. J., Beverley, S. M. (2007). Two Functionally Divergent UDP-Gal Nucleotide Sugar Transporters Participate in Phosphoglycan Synthesis in Leishmania major. J. Biol. Chem. 282: 14006-14017 [Abstract] [Full Text]  
  • Kleczka, B., Lamerz, A.-C., van Zandbergen, G., Wenzel, A., Gerardy-Schahn, R., Wiese, M., Routier, F. H. (2007). Targeted Gene Deletion of Leishmania major UDP-galactopyranose Mutase Leads to Attenuated Virulence. J. Biol. Chem. 282: 10498-10505 [Abstract] [Full Text]  
  • Konishi, T., Takeda, T., Miyazaki, Y., Ohnishi-Kameyama, M., Hayashi, T., O'Neill, M. A., Ishii, T. (2007). A plant mutase that interconverts UDP-arabinofuranose and UDP-arabinopyranose. Glycobiology 17: 345-354 [Abstract] [Full Text]  
  • Lamerz, A.-C., Haselhorst, T., Bergfeld, A. K., von Itzstein, M., Gerardy-Schahn, R. (2006). Molecular Cloning of the Leishmania major UDP-glucose Pyrophosphorylase, Functional Characterization, and Ligand Binding Analyses Using NMR Spectroscopy. J. Biol. Chem. 281: 16314-16322 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»