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Infection and Immunity, October 2002, p. 5684-5694, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5684-5694.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Relationship of the Glyoxylate Pathway to the Pathogenesis of Cryptococcus neoformans

Thomas H. Rude, Dena L. Toffaletti, Gary M. Cox, and John R. Perfect*

Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina

Received 20 May 2002/ Returned for modification 15 June 2002/ Accepted 12 July 2002

Functional genomics has become a major focus in the study of microbial pathogenesis. This study used a functional genomic tool, differential display reverse transcription-PCR, to identify a transcriptional profile of Cryptococcus neoformans cells as they produced meningitis in an immunosuppressed host. This serial global gene expression during infection allowed for the identification of up- and down-regulated genes during infection. During this profiling, a single gene for the enzyme isocitrate lyase (ICL1) was found to be up regulated at 1 week of infection in a rabbit meningitis model and during a time of maximum host cellular response. The finding suggested that this enzyme and the glyoxylate shunt pathway are important to this yeast's energy production during infection. However, site-directed icl1 mutants had no apparent virulence defect in two animal models and no growth defect within macrophages. These observations suggest that although the yeast responded to a certain environmental cue(s) by an increase in ICL1 expression during infection, this gene was not necessary for progression of a C. neoformans infection. Compounds that specifically target only ICL1 are unlikely to cripple C. neoformans growth in vivo.

* Corresponding author. Mailing address: Department of Medicine, Duke University Medical Center, P.O. Box 3353, Durham, NC 27710. Phone: (919) 684-4016. Fax: (919) 684-8902. E-mail: Perfe001{at}mc.duke.edu.

Editor: T. R. Kozel

Infection and Immunity, October 2002, p. 5684-5694, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5684-5694.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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