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Infect Immun. 2002 Oct;70(10):5684-94.

Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans.

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  • 1Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

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.

PMID:
12228298
[PubMed - indexed for MEDLINE]
PMCID:
PMC128360
Free PMC Article
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