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The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis

Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human host has not been attempted. Here, we extracted...

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Autores principales: Chen, Yuan, Toffaletti, Dena L., Tenor, Jennifer L., Litvintseva, Anastasia P., Fang, Charles, Mitchell, Thomas G., McDonald, Tami R., Nielsen, Kirsten, Boulware, David R., Bicanic, Tihana, Perfect, John R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950508/
https://www.ncbi.nlm.nih.gov/pubmed/24496797
http://dx.doi.org/10.1128/mBio.01087-13
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author Chen, Yuan
Toffaletti, Dena L.
Tenor, Jennifer L.
Litvintseva, Anastasia P.
Fang, Charles
Mitchell, Thomas G.
McDonald, Tami R.
Nielsen, Kirsten
Boulware, David R.
Bicanic, Tihana
Perfect, John R.
author_facet Chen, Yuan
Toffaletti, Dena L.
Tenor, Jennifer L.
Litvintseva, Anastasia P.
Fang, Charles
Mitchell, Thomas G.
McDonald, Tami R.
Nielsen, Kirsten
Boulware, David R.
Bicanic, Tihana
Perfect, John R.
author_sort Chen, Yuan
collection PubMed
description Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human host has not been attempted. Here, we extracted RNA from yeast cells taken directly from the cerebrospinal fluid (CSF) of two AIDS patients with cryptococcal meningitis prior to antifungal therapy. The patients were infected with strains of C. neoformans var. grubii of molecular type VNI and VNII. Using RNA-seq, we compared the transcriptional profiles of these strains under three environmental conditions (in vivo CSF, ex vivo CSF, and yeast extract-peptone-dextrose [YPD]). Although we identified a number of differentially expressed genes, single nucleotide variants, and novel genes that were unique to each strain, the overall expression patterns of the two strains were similar under the same environmental conditions. Specifically, yeast cells obtained directly from each patient’s CSF were more metabolically active than cells that were incubated ex vivo in CSF. Compared with growth in YPD, some genes were identified as significantly upregulated in both in vivo and ex vivo CSF, and they were associated with genes previously recognized for contributing to pathogenicity. For example, genes with known stress response functions, such as RIM101, ENA1, and CFO1, were regulated similarly in the two clinical strains. Conversely, many genes that were differentially regulated between the two strains appeared to be transporters. These findings establish a platform for further studies of how this yeast survives and produces disease.
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spelling pubmed-39505082014-03-12 The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis Chen, Yuan Toffaletti, Dena L. Tenor, Jennifer L. Litvintseva, Anastasia P. Fang, Charles Mitchell, Thomas G. McDonald, Tami R. Nielsen, Kirsten Boulware, David R. Bicanic, Tihana Perfect, John R. mBio Research Article Cryptococcus neoformans is the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the C. neoformans transcriptome in the human host has not been attempted. Here, we extracted RNA from yeast cells taken directly from the cerebrospinal fluid (CSF) of two AIDS patients with cryptococcal meningitis prior to antifungal therapy. The patients were infected with strains of C. neoformans var. grubii of molecular type VNI and VNII. Using RNA-seq, we compared the transcriptional profiles of these strains under three environmental conditions (in vivo CSF, ex vivo CSF, and yeast extract-peptone-dextrose [YPD]). Although we identified a number of differentially expressed genes, single nucleotide variants, and novel genes that were unique to each strain, the overall expression patterns of the two strains were similar under the same environmental conditions. Specifically, yeast cells obtained directly from each patient’s CSF were more metabolically active than cells that were incubated ex vivo in CSF. Compared with growth in YPD, some genes were identified as significantly upregulated in both in vivo and ex vivo CSF, and they were associated with genes previously recognized for contributing to pathogenicity. For example, genes with known stress response functions, such as RIM101, ENA1, and CFO1, were regulated similarly in the two clinical strains. Conversely, many genes that were differentially regulated between the two strains appeared to be transporters. These findings establish a platform for further studies of how this yeast survives and produces disease. American Society of Microbiology 2014-02-04 /pmc/articles/PMC3950508/ /pubmed/24496797 http://dx.doi.org/10.1128/mBio.01087-13 Text en Copyright © 2014 Chen et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Yuan
Toffaletti, Dena L.
Tenor, Jennifer L.
Litvintseva, Anastasia P.
Fang, Charles
Mitchell, Thomas G.
McDonald, Tami R.
Nielsen, Kirsten
Boulware, David R.
Bicanic, Tihana
Perfect, John R.
The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
title The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
title_full The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
title_fullStr The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
title_full_unstemmed The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
title_short The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
title_sort cryptococcus neoformans transcriptome at the site of human meningitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950508/
https://www.ncbi.nlm.nih.gov/pubmed/24496797
http://dx.doi.org/10.1128/mBio.01087-13
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