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Eukaryotic Cell, December 2003, p. 1336-1349, Vol. 2, No. 6
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.6.1336-1349.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

Biotechnology Laboratory, Department of Microbiology and Immunology, and Faculty of Agricultural Sciences, The University of British Columbia, Vancouver, British Columbia V6T 1Z3,¹ Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada,² Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710³

Received 9 August 2003/ Accepted 22 September 2003

Cryptococcus neoformans, an encapsulated basidiomycete fungus of medical importance, is capable of crossing the blood-brain barrier and causing meningitis in both immunocompetent and immunocompromised individuals. To gain insight into the adaptation of the fungus to the host central nervous system (CNS), serial analysis of gene expression (SAGE) was used to characterize the gene expression profile of C. neoformans cells recovered from the CNS of infected rabbits. A SAGE library was constructed, and 49,048 tags were sequenced; 16,207 of these tags were found to represent unique sequences or tag families. Of the 304 most-abundant tags, 164 were assigned to a putative gene for subsequent functional grouping. The results (as determined according to the number of tags that identified genes encoding proteins required for these functions) indicated that the C. neoformans cells were actively engaged in protein synthesis, protein degradation, stress response, small-molecule transport, and signaling. In addition, a high level of energy requirement of the fungal cells was suggested by a large number of tags that matched putative genes for energy production. Taken together, these findings provide the first insight into the transcriptional adaptation of C. neoformans to the host environment and identify the set of fungal genes most highly expressed during cerebrospinal fluid infection.