Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

Steen, B. R.; Zuyderduyn, S.; Toffaletti, D. L.; Marra, M.; Jones, S. J. M.; Perfect, J. R.; Kronstad, J.

doi:10.1128/ec.2.6.1336-1349.2003

Cited by 123Fungal Infections and StudiesFungal and yeast genetics researchBacterial Infections and Vaccines

Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

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Steen, B. R., Zuyderduyn, S., Toffaletti, D. L., Marra, M., Jones, S. J. M., Perfect, J. R., Kronstad, J.·2003·Eukaryotic Cell

DOI 10.1128/ec.2.6.1336-1349.2003PMC PMC326655

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Abstract

Cryptococcus neoformans, an encapsulated basidiomycete fungus of medical importance, is capable of crossing the blood-brain barrier and causing meningitis in both immunocompetent and immunocompromised individuals. To gain insight into the adaptation of the fungus to the host central nervous system (CNS), serial analysis of gene expression (SAGE) was used to characterize the gene expression profile of C. neoformans cells recovered from the CNS of infected rabbits. A SAGE library was constructed, and 49,048 tags were sequenced; 16,207 of these tags were found to represent unique sequences or tag families. Of the 304 most-abundant tags, 164 were assigned to a putative gene for subsequent functional grouping. The results (as determined according to the number of tags that identified genes encoding proteins required for these functions) indicated that the C. neoformans cells were actively engaged in protein synthesis, protein degradation, stress response, small-molecule transport, and signaling. In addition, a high level of energy requirement of the fungal cells was suggested by a large number of tags that matched putative genes for energy production. Taken together, these findings provide the first insight into the transcriptional adaptation of C. neoformans to the host environment and identify the set of fungal genes most highly expressed during cerebrospinal fluid infection.

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Copper concentrations vary widely in different tissues within a mammalian host.
“the copper transporter gene CTR4 is expressed by C. neoformans at a constant low level in fungus growing in the lungs of mice, but is expressed at a high level in fungus isolated from the central nervous system due to the different physiological copper concentrations present at these sites (Steen et al. 2003; Ding et al. 2013).”
From Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence (2022) · cites this paper as Steen et al. 2003
Hsp90 is naturally abundant in fungal cells and is induced to even greater levels by heat shock and other proteotoxic stresses.
“Hsp90 is naturally abundant in fungal cells and is induced to even greater levels by heat shock and other proteotoxic stresses10,15,32-35.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [33]
Hsp90 levels increase following environmental challenges.
“Furthermore, although Hsp90 levels increase following environmental challenges, Hsp90 activity is tightly controlled via post-translational regulation and an autoregulatory loop involving the heat shock transcription factor, Hsf1.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [33]

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Authors: Steen, B. R., Zuyderduyn, S., Toffaletti, D. L., Marra, M., Jones, S. J. M., Perfect, J. R., & Kronstad, J.
Affiliations: University of British Columbia (CA)
BC Cancer Agency (CA)
Corresponding author: Kronstad, J.
ORCID: Toffaletti, D. L.
Marra, M.
Jones, S. J. M.
Perfect, J. R.
Kronstad, J.
Venue: Eukaryotic Cell
Publisher: American Society for Microbiology
Published: 2003-12
Volume: 2
Issue: 6
Pages: 1336-1349
ISSN: 1535-9778 (ISSN-L)
1535-9786
DOI: 10.1128/ec.2.6.1336-1349.2003
PMC: PMC326655
OpenAlex: W2158372574
Cited by: 123
References: 102
Citations by year: 2026: 3 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 19 · 2013: 8 · 2012: 4
FWCI: 5.14
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Eukaryotic Cell (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Burroughs Wellcome Fund
University of Oklahoma
Michael Smith Health Research BC
Canadian Institutes of Health Research
National Institute of Allergy and Infectious Diseases (R56AI028388, AI28388, R01AI028388)
Topics: Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords: Cryptococcus neoformans, cryptococcal meningitis, gene expression profiling, serial analysis of gene expression, blood-brain barrier penetration, central nervous system adaptation, cerebrospinal fluid infection, rabbit model, stress response, energy metabolism, protein synthesis, small molecule transport
MeSH terms: Animals, Cerebrospinal Fluid, Cryptococcus neoformans, Genes, Fungal, Rabbits, Gene Library, Gene Expression Regulation, Fungal, Databases, Factual, Meningitis, Cryptococcal, Expressed Sequence Tags, Gene Expression Profiling

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Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

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