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Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans.
- Source :
-
Infection and immunity [Infect Immun] 2002 Oct; Vol. 70 (10), pp. 5684-94. - Publication Year :
- 2002
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cryptococcosis etiology
Cryptococcus neoformans genetics
Cryptococcus neoformans growth & development
DNA, Fungal genetics
Female
Fungal Proteins genetics
Fungal Proteins metabolism
Gene Expression
Genes, Fungal
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
Cryptococcus neoformans metabolism
Cryptococcus neoformans pathogenicity
Glyoxylates metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0019-9567
- Volume :
- 70
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 12228298
- Full Text :
- https://doi.org/10.1128/IAI.70.10.5684-5694.2002