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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rude, TH; Toffaletti, DL; Cox, GM; Perfect, JR

Published Date

  • October 2002

Published In

Volume / Issue

  • 70 / 10

Start / End Page

  • 5684 - 5694

PubMed ID

  • 12228298

Pubmed Central ID

  • 12228298

International Standard Serial Number (ISSN)

  • 0019-9567

Digital Object Identifier (DOI)

  • 10.1128/iai.70.10.5684-5694.2002

Language

  • eng

Conference Location

  • United States