HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans
Ontology highlight
ABSTRACT:
ORGANISM(S): Cryptococcus neoformans
PROVIDER: GSE22988 | GEO | 2011/04/13
SECONDARY ACCESSION(S): PRJNA127769
REPOSITORIES: GEO
Similar Datasets
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
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
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
Project description:The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.
| S-EPMC2991262 | biostudies-literature
Project description:The opportunistic pathogen Cryptococcus neoformans causes fungal meningoencephalitis in immunocompromised individuals. In previous studies, we found that the Hap complex in this pathogen represses genes encoding mitochondrial respiratory functions and TCA cycle components under low-iron conditions. The orthologous Hap2/3/4/5 complex in Saccharomyces cerevisiae exerts a regulatory influence on mitochondrial functions and Hap4 is subject to glucose repression via the carbon catabolite repressor Mig1. In this study, we explored the regulatory link between a candidate ortholog of the Mig1 protein and the HapX component of the Hap complex in C. neoformans. This analysis revealed repression of MIG1 by HapX and activation of HAPX by Mig1 in low iron conditions, and Mig1 regulation of mitochondrial functions including respiration, tolerance for reactive oxygen species, and expression of genes for iron-consuming and iron-acquisition functions. Consistent with these regulatory functions, a mig1Î mutant had impaired growth on inhibitors of mitochondrial respiration and ROS inducers. Furthermore, deletion of MIG1 provoked a dysregulation in nutrient sensing via the TOR pathway and impacted the pathway for cell wall remodeling. Importantly, loss of Mig1 increased susceptibility to fluconazole thus further establishing a link between azole antifungal drugs and mitochondrial function. Mig1 and HapX were also required together for survival in macrophages, but Mig1 alone had a minimal impact on virulence in mice. Overall, these studies provide novel insights into a HapX/Mig1 regulatory network and reinforce an association between mitochondrial dysfunction and drug susceptibility that may provide new targets for the development of antifungal drugs. In this study, transcription profiles of WT and mig1D mutant strains of Cryptococcus neoformans were compared in a dye-swap experiment following 6hr exposure to Low Iron Medium (LIM) or LIM + 100mM FeCl3.
2015-12-17 | E-GEOD-76063 | 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:The opportunistic pathogen Cryptococcus neoformans causes fungal meningoencephalitis in immunocompromised individuals. In previous studies, we found that the Hap complex in this pathogen represses genes encoding mitochondrial respiratory functions and TCA cycle components under low-iron conditions. The orthologous Hap2/3/4/5 complex in Saccharomyces cerevisiae exerts a regulatory influence on mitochondrial functions and Hap4 is subject to glucose repression via the carbon catabolite repressor Mig1. In this study, we explored the regulatory link between a candidate ortholog of the Mig1 protein and the HapX component of the Hap complex in C. neoformans. This analysis revealed repression of MIG1 by HapX and activation of HAPX by Mig1 in low iron conditions, and Mig1 regulation of mitochondrial functions including respiration, tolerance for reactive oxygen species, and expression of genes for iron-consuming and iron-acquisition functions. Consistent with these regulatory functions, a mig1Δ mutant had impaired growth on inhibitors of mitochondrial respiration and ROS inducers. Furthermore, deletion of MIG1 provoked a dysregulation in nutrient sensing via the TOR pathway and impacted the pathway for cell wall remodeling. Importantly, loss of Mig1 increased susceptibility to fluconazole thus further establishing a link between azole antifungal drugs and mitochondrial function. Mig1 and HapX were also required together for survival in macrophages, but Mig1 alone had a minimal impact on virulence in mice. Overall, these studies provide novel insights into a HapX/Mig1 regulatory network and reinforce an association between mitochondrial dysfunction and drug susceptibility that may provide new targets for the development of antifungal drugs.
2015-12-17 | GSE76063 | GEO
Project description:Proper mitochondrial function is critical for the ability of the fungal pathogen Cryptococcus neoformans to cause disease. Mitochondrial dysfunction of WT cells treated with antimycin A or L-DOPA, or on cells lacking Cir1 is evident from this dataset. These experiments revealed influences on transcript levels of genes encoding Fe-S cluster assembly components and the response to oxidative stress in Cryptococcus neoformans.
2024-04-07 | GSE222564 | GEO
Project description:HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans
| PRJNA127769 | ENA
Project description:Cryptococcus neoformans is an invasive human fungal pathogen, which causes pneumonia and meningoencephalitis in both healthy and immunodeficient individuals, resulting 181,100 deaths each year. Studies have demonstrated that copper detoxification machineries play critical functions in modulating C. neoformans fitness and pathogenicity in the host lung tissue. Pulmonary C. neoformans infection provokes the generation of toxic copper bombardment, which in return activate detoxification process in fungal cells. However, the molecular mechanism on how Cu inhibits C. neoformans in proliferation remains unclear. Here, using Cu detoxification gene knockout strains we demonstrated that exogenous Cu ions inhibit cell growth of the metallothionein mutant, which was significantly rescue when supplementing with the ROS scavenger, N-acetylcysteine. To future characterize the molecular mechanism of C. neoformans response to Cu toxicity, we employ iTRAQ with LC-MS/MS analysis, in the presence of exogenous Cu or NAC. Our data showed that an increased Cu level repressed expression of factors involved in protein translation but activates expression of important players in ubiquitin-degradation process. We proposed that the downregulation of protein synthesis and the upregulation of protein degradation were the main strategy of Cu toxicity. The metallothionein mutant showed a higher ubiquitination level under Cu treatment. In addition, MG132 could partially restore the Cu toxicity effect on metallothionein mutant. These results shed new light on the Cu antifungal mechanisms from proteomic profile.
2021-02-09 | PXD024098 |