Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans

Infect Immun. 2002 Oct;70(10):5684-94. doi: 10.1128/IAI.70.10.5684-5694.2002.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cryptococcosis / etiology
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / growth & development
  • Cryptococcus neoformans / metabolism*
  • Cryptococcus neoformans / pathogenicity*
  • DNA, Fungal / genetics
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression
  • Genes, Fungal
  • Glyoxylates / metabolism*
  • Humans
  • Isocitrate Lyase / genetics
  • Isocitrate Lyase / metabolism
  • Macrophages / microbiology
  • Meningitis, Cryptococcal / etiology
  • Mice
  • Mice, Inbred A
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Rabbits
  • Sequence Homology, Amino Acid
  • Virulence / genetics
  • Virulence / physiology


  • DNA, Fungal
  • Fungal Proteins
  • Glyoxylates
  • Isocitrate Lyase
  • glyoxylic acid

Associated data

  • GENBANK/AF455253