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Eukaryotic Cell, December 2004, p. 1601-1608, Vol. 3, No. 6
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.6.1601-1608.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

UGD1, Encoding the Cryptococcus neoformans UDP-Glucose Dehydrogenase, Is Essential for Growth at 37°C and for Capsule Biosynthesis{dagger}

Frédérique Moyrand and Guilhem Janbon*

Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France

Received 14 September 2004/ Accepted 13 October 2004

We report the identification and disruption of the Cryptococcus neoformans var. grubii UGD1 gene encoding the UDP-glucose dehydrogenase, which catalyzes the conversion of UDP-glucose into UDP-glucuronic acid. Deletion of UGD1 led to modifications in the cell wall, as revealed by changes in the sensitivity of ugd1{Delta} cells to sodium dodecyl sulfate, NaCl, and sorbitol. Moreover, two of the yeast's major virulence factors—capsule biosynthesis and the ability to grow at 37°C—were impaired in ugd1{Delta} strains. These results suggest that the UDP-dehydrogenase represents the major, and maybe only, biosynthetic pathway for UDP-glucuronic acid in C. neoformans. Consequently, deletion of UGD1 blocked not only the synthesis of UDP-glucuronic acid but also that of UDP-xylose. To differentiate the phenotype(s) associated with the UDP-glucuronic acid defect alone from those linked to the UDP-xylose defect, ugd1{Delta} mutants were phenotypically compared to strains from which the gene encoding UDP-xylose synthase (i.e., that required for synthesis of UDP-xylose) had been deleted. Finally, studies of strains from which one of the four CAP genes (CAP10, CAP59, CAP60, or CAP64) had been deleted revealed common cell wall phenotypes associated with the acapsular state.

* Corresponding author. Mailing address: Unité de Mycologie Moléculaire, Institut Pasteur, 25 rue du Dr-Roux, F-75724 Paris Cedex 15, France. Phone: 33 1 45688356. Fax: 33 1 45688420. E-mail: janbon{at}pasteur.fr.

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

Eukaryotic Cell, December 2004, p. 1601-1608, Vol. 3, No. 6
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.6.1601-1608.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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