How host-like signals drive gene expression and gene expression drives capsule growth in Cryptococcus neoformans [ep_pert]
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ABSTRACT:
ORGANISM(S): Cryptococcus neoformans var. grubii
PROVIDER: GSE226651 | GEO | 2023/08/02
REPOSITORIES: GEO
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Project description:Cryptococcus neoformans is a fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and during in vitro growth in response to host-like conditions. To understand how individual host-like signals affect capsule size and gene expression, we grew cells wild-type KN99 cells with either no added cyclic AMP (cAMP), 1.1 mM, 1.8 mM, 3.3 mM, 11 mM, or 20 mM cAMP. capsule thickness at 1440 min. We also took samples for RNA-Seq at 30, 90, 180, 1440 minutes and carried out RNA-Seq in quadruplicate. We also measured capsule thickness at 1440 min.
2023-08-02 | GSE226637 | GEO
Project description:Cryptococcus neoformans is a fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and during in vitro growth in response to host-like conditions. To understand how individual host-like signals affect capsule size and gene expression, we grew cells with and without all combinations of 5 signals suspected of affecting capsule size: Tissue-culture medium (DMEM or RPMI), temperature (37°C), CO2 (5%), and the addition of HEPES buffer. For each combination of conditions, we grew cultures with or without exogenous cAMP, and sampled cells for RNA-Seq at 0, 30, 90, 180, 1440 minutes and for measurement of capsule thickness at 1440 min. We also took samples for RNA-Seq at 30, 90, 180, 1440 minutes and carried out RNA-Seq in quadruplicate.
2023-08-02 | GSE226255 | GEO
Project description:Cryptococcus neoformans is an opportunistic basidiomycete pathogen that is a major etiological agent of fungal meningoencephalitis leading to more than 180,000 deaths worldwide annually. For this pathogen, the polysaccharide capsule is a key virulence factor, which interferes with the phagocytosis by host innate immune cells, but its complex signaling networks remain elusive. In this study, we systematically analyzed capsule biosynthesis and signaling networks by using C. neoformans transcription factor (TF) and kinase mutant libraries under diverse capsule-inducing conditions, such as Dulbecco’s Modified Eagle’s (DME), Littman’s medium (LIT) and fetal bovine serum (FBS) medium. We found that deletion of GAT201, YAP1, BZP4, and ADA2 consistently causes capsule production defects in all tested media, indicating that they are capsule-regulating core TFs. Epistatic and expression analysis showed that Yap1 and Ada2 control Gat201 upstream, whereas Bzp4 and Gat201 regulate capsule production independently. We next searched for potential upstream kinases and found that mutants deleted of PKA1, BUD32, POS5, IRE1 or CDC2801 showed reduced capsule production under all three capsule induction conditions, whereas mutants deleted of HOG1 and IRK5 displayed enhanced capsule production. Notably, Pka1 and Irk5 controls induction of GAT201 and BZP4, respectively, under capsule induction condition. Finally, we monitored transcriptome profiles governed by Bzp4, Gat201, and Ada2 under capsule-inducing condition and demonstrated that these TFs regulate redundant and unique sets of downstream target genes. In conclusion, this study provides further insight into the complex regulatory mechanism of capsule production related signaling pathways in C. neoformans.
2022-10-18 | GSE208163 | GEO
Project description:Cryptococcus neoformans causes meningoencephalitis and is an increasing human health threat. C. neoformans is neurotropic, and persists in the cerebrospinal fluid (CSF) of the mammalian host during infection. In order to survive in the host, pathogenic fungi must procure nutrients such as carbon and nitrogen. To enhance our understanding of nutrient acquisition during infection by Cryptococcus species, we examined utilization of nitrogen sources available in CSF. We screened for growth and capsule production of 817 global environmental and clinical isolates on various sources of nitrogen. Capsule production was assessed using ammonium and urea in the presence or absence of benomyl to determine the relationship of urea exposure to capsule production. Since urea is metabolized to ammonia and CO2 (a known signal for capsule induction), we examined urea metabolism mutants for their response to urea regarding capsule production. Non-preferred nitrogen sources were found to greatly affect capsule production in pathogenic species of Cryptococcus. Urea induced the greatest magnitude of capsule production. Capsule induction by urea was greater in Cryptococcus gattii strains than in C. neoformans strains. In addition, both environmental and clinical strains grew robustly on uric acid, casamino acids, creatinine, and asparagine as sole nitrogen sources. While substantial growth on nitrate was not apparent at day 3, growth was apparent by day 6 for all serotypes.
2013-09-25 | GSE46829 | GEO
Project description:Cryptococcus neoformans causes meningoencephalitis and is an increasing human health threat. C. neoformans is neurotropic, and persists in the cerebrospinal fluid (CSF) of the mammalian host during infection. In order to survive in the host, pathogenic fungi must procure nutrients such as carbon and nitrogen. To enhance our understanding of nutrient acquisition during infection by Cryptococcus species, we examined utilization of nitrogen sources available in CSF. We screened for growth and capsule production of 817 global environmental and clinical isolates on various sources of nitrogen. Capsule production was assessed using ammonium and urea in the presence or absence of benomyl to determine the relationship of urea exposure to capsule production. Since urea is metabolized to ammonia and CO2 (a known signal for capsule induction), we examined urea metabolism mutants for their response to urea regarding capsule production. Non-preferred nitrogen sources were found to greatly affect capsule production in pathogenic species of Cryptococcus. Urea induced the greatest magnitude of capsule production. Capsule induction by urea was greater in Cryptococcus gattii strains than in C. neoformans strains. In addition, both environmental and clinical strains grew robustly on uric acid, casamino acids, creatinine, and asparagine as sole nitrogen sources. While substantial growth on nitrate was not apparent at day 3, growth was apparent by day 6 for all serotypes. In this study, transcription profiles of urea pathway mutants (ure1 and amt1/2) and WT Cryptococcus neoformans strains were compared in a dye-swap experiment following 1hr exposure to proline or proline + urea (.25g/L).
2013-09-25 | E-GEOD-46829 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE31911: Cryptococcal H99 cells grown in 8 conditions for capsule induction GSE32049: RNA-Seq analysis of ada2?, nrg1? and cir1? and KN99? wildtype cells in capsule inducing and non-inducing conditions GSE32075: ChIP-Seq of H3K9 acetylation for wildtype and ada2? cells in Cryptococcus neoformans Refer to individual Series
2011-12-10 | E-GEOD-32228 | biostudies-arrayexpress
Project description:We compared the transcriptome of subpopulations of Cryptococcus neoformans cells within the lungs and C. neoformans cells cultured in capsule repressing medium, capsule inducing medium, and capsule inducing medium with the addition of 10% conditioned medium from cells grown in capsule repressing medium. The aim of the study was to identify genes that regulate C. neoformans cell body and capsule size reductions.
2022-01-01 | GSE152784 | GEO
Project description:Fungal diseases are critical burdens on the global healthcare system, infecting over 25% of the world’s population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis; a disease enabled by elaboration of sophisticated virulence factors, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes in the presence of the host. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. Building upon knowledge of zinc transport regulation at the transcriptional level, here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe distinct protein-level responses to zinc-limited and -excess conditions through a shift of the proteome profile towards stress response and metal acquisition, including the upregulation of the zinc transporter, ZIP1. In addition, we reveal a novel connection among zinc availability, protein folding, capsule production, and virulence through the detection of a Wos2-like ortholog in the secretome under replete conditions. Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc availability and fungal virulence. These findings support the development of new antifungal strategies focused on the enhancement of nutritional immunity within the host.
2022-02-16 | PXD023204 | Pride
Project description:Cryptococcus neoformans is a human fungal pathogen found ubiquitously within the environment and associated with infection of primarily immunocompromised individuals. Without the activation of an effective immune response, the pathogen can survive, proliferate, and disseminate throughout the host through the action of diverse virulence factors. These virulence factors include a polysaccharide capsule to protect the fungus from phagocytosis by macrophages, melanin production to neutralize reactive oxygen species, thermotolerance to survive at human physiological temperatures, and extracellular enzymes for host tissue degradation and invasion. We previously used mass spectrometry-based proteomics to explore the production of fungal virulence factors during infection using in vitro (macrophages) and in vivo (murine) models of disease. Based on our studies, we investigated the proteome response of C. neoformans upon disruption of CipC, a virulence-associated fungal protein.
2024-10-13 | PXD056761 | Pride
Project description:We measured protein translation (by ribosome profiling) and RNA levels (by polyA-enriched RNA-seq) in Cryptococcus neoformans strain H99 and Cryptococcus neoformans strain JEC21. This is the first transcriptome-wide map of translation in this species complex.
2019-06-22 | GSE133125 | GEO