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The Cryptococcus neoformans transcriptome at the site of human meningitis.

Chen, Y; Toffaletti, DL; Tenor, JL; Litvintseva, AP; Fang, C; Mitchell, TG; McDonald, TR; Nielsen, K; Boulware, DR; Bicanic, T; et al. Chen, Y; Toffaletti, DL; Tenor, JL; Litvintseva, AP; Fang, C; Mitchell, TG; McDonald, TR; Nielsen, K; Boulware, DR; Bicanic, T; Perfect, JR (2014) The Cryptococcus neoformans transcriptome at the site of human meningitis. MBio, 5 (1). e01087 - e01013. https://doi.org/10.1128/mBio.01087-13
SGUL Authors: Bicanic, Tihana

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Abstract

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.

Item Type: Article
Additional Information: Copyright © 2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: MBio
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Dates:
DateEvent
4 February 2014Published
PubMed ID: 24496797
Web of Science ID: 24496797
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URI: https://openaccess.sgul.ac.uk/id/eprint/105178
Publisher's version: https://doi.org/10.1128/mBio.01087-13

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