| UDP-glucose dehydrogenase plays multiple roles in the biology of the pathogenic fungus Cryptococcus neoformans. | |
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MedLine Citation:
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PMID: 15383535 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cryptococcus neoformans is a pathogenic fungus surrounded by an elaborate polysaccharide capsule that is strictly required for its virulence in humans and other mammals. Nearly half of the sugar residues in the capsule are derived from UDP-glucuronic acid or its metabolites. To examine the role of these nucleotide sugars in C. neoformans, the gene encoding UDP-glucose dehydrogenase was disrupted. Mass spectrometry analysis of nucleotide sugar pools showed that the resulting mutant lacked both UDP-glucuronic acid and its downstream product, UDP-xylose, thus confirming the effect of the knockout and indicating that an alternate pathway for UDP-glucuronic acid production was not used. The mutant was dramatically affected by the lack of specific sugar donors, demonstrating altered cell integrity, temperature sensitivity, lack of growth in an animal model of cryptococcosis, and morphological defects. Additionally, the polysaccharide capsule could not be detected on the mutant cells, although the possibility remains that abbreviated forms of capsule components are made, possibly without proper surface display. The capsule defect is largely independent of the other observed changes, as cells that are acapsular because of mutations in other genes show lack of virulence but do not exhibit alterations in cell integrity, temperature sensitivity, or cellular morphology. All of the observed alterations were reversed by correction of the gene disruption. |
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Authors:
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Cara L Griffith; J Stacey Klutts; Lijuan Zhang; Steven B Levery; Tamara L Doering |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2004-09-21 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 279 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-25 Completed Date: 2005-01-11 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 51669-76 Citation Subset: IM |
Affiliation:
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Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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chemistry Cell Membrane / metabolism Chromatography, High Pressure Liquid Coloring Agents / pharmacology Cryptococcus neoformans / physiology* DNA / chemistry Genetic Complementation Test Glucuronic Acid / chemistry Immunoblotting Mass Spectrometry Microscopy, Electron Microscopy, Electron, Transmission Microscopy, Fluorescence Microscopy, Interference Models, Genetic Mutation Nucleotides / chemistry Polysaccharides / chemistry Protein Binding Temperature Uridine Diphosphate Glucose Dehydrogenase / genetics*, physiology* Uridine Diphosphate Xylose / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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GM F32 072341/GM/NIGMS NIH HHS; GM R01 066303/GM/NIGMS NIH HHS; GM R01 069968/GM/NIGMS NIH HHS; P20 RR16459/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Coloring Agents; 0/Nucleotides; 0/Polysaccharides; 3616-06-6/Uridine Diphosphate Xylose; 576-37-4/Glucuronic Acid; 9007-49-2/DNA; EC 1.1.1.22/Uridine Diphosphate Glucose Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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