Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differentially expressed genes of cir1 mutants in low iron or high iron medium

ABSTRACT: Iron overload is known to exacerbate many infectious diseases and, conversely, iron withholding is an important defense strategy for mammalian hosts. The mechanisms by which fungal pathogens sense iron in the mammalian host environment are poorly understood. The AIDS-associated pathogen Cryptococcus neoformans provides a unique opportunity to explore iron sensing in the context of infection because iron levels control elaboration of the polysaccharide capsule that is the major virulence factor of the fungus. Additionally, excess iron exacerbates experimental cryptococcosis. We identified the iron-responsive transcription factor Cir1 that regulates iron acquisition in C. neoformans and discovered that Cir1 also controls the expression of all of the known major virulence factors of the fungus. In particular, cir1 mutants are defective in capsule formation and avirulent in a mouse model of cryptococcosis. Thus the ability to sense iron is critical during infection by C. neoformans and may represent a target for antifungal therapy. Keywords: wt/mutant x low/high iron

ORGANISM(S): Cryptococcus neoformans var. neoformans Cryptococcus neoformans var. neoformans B-3501A

PROVIDER: GSE5341 | GEO | 2006/09/14

SECONDARY ACCESSION(S): PRJNA96195

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

ChIP-Seq analysis of the iron regulatory transcription factors in Cryptococcus neoformans in response to iron availability

Project description:Purpose: Defining the regulatory role of the transcription factors, Cir1 and HapX, in C. neoformans. Methods: Chromatin immunoprecipitation followed by high-throughput sequencing was performed using chromatin immunoprecipitated DNA from the strains Cir1-Flag and HapX-Flag grown in low- and high-iron condition. Results: Cir1 and HapX bind to the promoter region of the genes involved in iron acquisition and metabolism in C. neoformans.

2020-02-16 | GSE126312 | GEO

Transcriptome analysis of the iron regulatory transcription factors in Cryptococcus neoformans in response to iron availability

Project description:Purpose: Understanding the iron-responsive regulatory networks in Cryptococcus neoformans. Methods: The transcriptome profiles of the wild-type, cir1 mutant and hapX mutant were generated by RNA-seq using Illumina Hiseq, in triplicate. The transcriptome profiles of each mutant was compared with that of the wild-type strain. Results: The iron-responsive transcription factors, Cir1 and HapX, are major regulators for iron acquisition and metabolism in C. neoformans.

2020-02-16 | GSE126313 | GEO

HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans

Project description:Analysis of the transcriptional response of C. neoformans WT, cir1 mutant, hap3 mutant and hapX mutant to different iron sources.

2011-04-13 | GSE22988 | GEO

HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans

Project description:Analysis of the transcriptional response of C. neoformans WT, cir1 mutant, hap3 mutant and hapX mutant to different iron sources. The following experimental design was adopted for the study. Within each strain, each treatment pair (low-iron, +FeCl3, +Transferrin and +Hemin; 6 pairs) were hybridized to an array; and within each treatment, each strain (WT, hap3, hapX and cir1, 6 pairs) were hybridized to an array for a total of 48 microarrays. Each strain/treatment combination was labeled an equal number of times with Cy3 and Cy5 to ensure dye balance

2011-04-13 | E-GEOD-22988 | biostudies-arrayexpress

WT vs rim101 mutant gene expression under capsule inducing conditions

Project description:Cryptococcus neoformans is a prevalent human fungal pathogen that must survive within various tissues in order to establish a human infection. We have identified the C. neoformans Rim101 transcription factor, a highly conserved pH-response regulator in many fungal species. The rim101- mutant strain displays growth defects similar to other fungal species in the presence of alkaline pH, increased salt concentrations, and iron limitation. However, the rim101- strain is also characterized by a striking defect in capsule, an important virulence-associated phenotype. This capsular defect is likely due to alterations in polysaccharide attachment to the cell surface, not in polysaccharide biosynthesis. In contrast to many other C. neoformans capsule-defective strains, the rim101- mutant is hypervirulent in animal models of cryptococcosis. Whereas Rim101 activation in other fungal species occurs through the conserved Rim pathway, we demonstrate that C. neoformans Rim101 is also activated by the cAMP/PKA pathway. We report here that C. neoformans uses PKA and the Rim pathway to regulate the localization, activation, and processing of the Rim101 transcription factor. We also demonstrate specific host- relevant activating conditions for Rim101 cleavage, showing that C. neoformans has co-opted conserved signaling pathways to respond to the specific niche within the infected host. These results establish a novel mechanism for Rim101 activation and the integration of two conserved signaling cascades in response to host environmental conditions.

2010-09-04 | GSE23929 | GEO

Toward an integrated model of capsule regulation in Cryptococcus neoformans

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

Zinc-associated proteome of Cryptococcus neoformans

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

Mrj1HA AP-MS in Cryptococcus neoformans

Project description:The opportunistic fungal pathogen Cryptococcus neoformans must adapt to the mammalian environment to establish an infection. Proteins facilitating adaptation to novel environments, such as chaperones, may be required for virulence. In this study, we identified a novel mitochondrial co-chaperone, Mrj1, necessary for virulence in C. neoformans. The mrj1∆ and J-domain inactivated mutants had general growth defects, and were deficient in two major virulence factors, thermotolerance and capsule elaboration. The latter phenotype was associated with cell wall changes and increased capsular polysaccharide shedding. Accordingly, the mrj1∆ mutant was avirulent in a murine model of cryptococcosis. Mrj1 has a mitochondrial localization and co-immunoprecipitated with Qcr2, a core component of complex III of the ETC (Electron Transport Chain). The mrj1 mutants were deficient in mitochondrial functions including growth on alternative carbon sources, growth without iron, and mitochondrial polarization. They were also insensitive to complex III inhibitors and hypersensitive to an alternative oxidase (AOX) inhibitor suggesting that Mrj1 functions in respiration. In support of this conclusion, mrj1 mutants also had elevated basal oxygen consumption rates which were completely abolished by the addition of the AOX inhibitor, confirming that Mrj1 is required for mitochondrial respiration through complexes III and IV. Furthermore, inhibition of complex III phenocopied the capsule and cell wall defects of the mrj1 mutants. Taken together, these results indicate that Mrj1 is required for normal mitochondrial respiration, a key aspect of adaptation to the host environment and virulence.

2020-06-12 | PXD013659 | Pride

WT vs gcn5 mutant gene expression under capsule inducing conditions

Project description:Cryptococcus neoformans is an environmental fungus and an opportunistic human pathogen. Previous studies have demonstrated major alterations in its transcriptional profile as this microorganism enters the hostile environment of the human host. To assess the role of chromatin remodeling in host-induced transcriptional responses, we identified the C. neoformans Gcn5 histone acetyltransferase and demonstrated its function by complementation studies of Saccharomyces cerevisiae. The C. neoformans gcn5Δ mutant strain has defects in high-temperature growth and capsule attachment to the cell surface, in addition to increased sensitivity to FK506 and oxidative stress. Treatment of wild-type cells with the histone acetyltransferase inhibitor garcinol mimics cellular effects of the gcn5Δ mutation. Gcn5 regulates the expression of many genes that are important in responding to the specific environmental conditions encountered by C. neoformans inside the host. Accordingly, the gcn5Δ mutant is avirulent in animal models of cryptococcosis. Our study demonstrates the importance of chromatin remodeling by the conserved histone acetyltransferase Gcn5 in regulating the expression of specific genes that allow C. neoformans to respond appropriately to the human host.

2010-09-04 | GSE23948 | GEO

Proteomic profiling of Cryptococcus neoformans

Project description:The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors including capsule and melanin is in part regulated by the cyclic-AMP/Protein Kinase A (PKA) signal transduction pathway. In this study, we investogated the influence of PKA on the composition of the intracellular proteome to obatin a comprehensive understanding of the regulation that underpins virulence. Through quantitative proteomics, enrichment and bioinformatic analyses, and an interactome study, we discovered a conserved pattern of PKA regulation for proteins associated with translation, the proteasome, metabolism, amino acid biosynthesis, and virulence-related functions. PKA regulation of the ubiquitin-proteasome pathway in C. neoformans showed a striking parallel with connections between PKA and protein degradation in chronic neurodegenerative disorders and other human diseases. Further investigation using the proteasome inhibitor bortezomib revealed an impact on capsule production and fungal growth. These results prompted additional studies of the antifungal activity of bortezomib in the context of cAMP signlaing and in combination with fluconazole. Taken together, the data suggest a model whereby PKA activation causes a shift in proteostasis and the function of the endoplasmic reticulum to support the synthesis and export of capsule polysaccharide. Overall, this study revealed a remarkably broad and conserved influence of the cAMP/PKA pathway on the proteome, and identified proteostasis as a potential therapeutic target for the treatment of cryptococcosis.

2016-01-18 | PXD002727 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data