Rdi1∆ vs WT during macrophage co-culture
Ontology highlight
ABSTRACT:
ORGANISM(S): Cryptococcus neoformans var. grubii H99 Cryptococcus neoformans var. neoformans
PROVIDER: GSE8688 | GEO | 2009/05/28
SECONDARY ACCESSION(S): PRJNA101905
REPOSITORIES: GEO
Similar Datasets
Project description: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
2006-09-14 | GSE5341 | GEO
Project description:Systemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments of cryptococcosis are available. Here, we describe Prm1, a novel regulator of virulence in C. neoformans. C. neoformans prm1 cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, prm1 cells show deficiencies in the biosynthesis of chitin, chitosan, and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed prm1 cells was found to facilitate the host immunological defence against infection with wild-type C. neoformans. Further investigation demonstrated that prm1 cells strongly promote pulmonary production of interferon- and Th1 responses, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that C. neoformans Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.
2023-10-11 | PXD038840 | Pride
Project description:Ubiquitination is a reversible protein modification involved in various cellular processes in eukaryotic cells. Deubiquitinating enzymes, the proteins responsible for the removal of ubiquitin, act as essential regulators to maintain ubiquitin homeostasis and to exquisitely regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily within the immunocompromised population. In order to understand the possible influence deubiquitinating enzymes have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of 7 putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5M-bM-^HM-^F mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 appears to be the major deubiquitinating enzyme in C. neoformans for maintaining a pool of free ubiquitin for stress responses, supports the evolutionary divergence of Cryptococcus sp. from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. In addition, other putative deubiquitinase mutants (doa4M-bM-^HM-^F and ubp13M-bM-^HM-^F) exhibit similar phenotypes to the ubp5M-bM-^HM-^F mutant, illustrating possible functional overlap among deubiquitinating enzymes in C. neoformans. Certain functioning deubiquitinating enzymes are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host. In this study, transcription profiles of ubp5 mutant and WT Cryptococcus neoformans strains were compared in a dye-swap experiment following 1hr exposure to either 30C or 37C.
2012-04-10 | E-GEOD-35067 | biostudies-arrayexpress
Project description:A family of APSES transcription factor is known to be fungal-specific transcriptional regulators and play important roles in governing growth, differentiation, and virulence of diverse fungal pathogens. Yet none of APSES-like transcription factors have been identified and investigated in a basidiomycetous fungal pathogen, Cryptococcus neoformans. In the present study we discovered an APSES-like transcription factor, mbs1 (Mbp1/Swi4-like APSES protein 1), as one of novel flucytosine-responsive genes (total 194 genes) identified through comparative transcriptome analysis of C. neoformans hybrid sensor kinase mutants, tco1 and tco2 mutants, which displayed differential flucytosine-susceptibility. Supporting the microarray data, Northern blot and quantitative RT-PCR analysis confirmed that expression of mbs1 is rapidly induced in response to flucytosine in the wild-type strain, but not in the tco1 and tco2 mutants. Furthermore, C. neoformans with deletion of the mbs1 gene exhibited increased susceptibility to flucytosine. Intriguingly, mbs1 plays pleiotropic roles in diverse cellular process of C. neoformans. mbs1 positively regulates ergosterol biosynthesis and thereby its inhibition confers increased susceptibility and resistance to amphotericin B and azole drugs, respectively. mbs1 is also involved in DNA damage repair counteracting genotoxic stresses. During sexual differentiation mbs1 represses pheromone production, but promotes cell-cell fusion. Furthermore mbs1 is required for production of antioxidant melanin pigment and full virulence of C. neoformans. Finally we also performed DNA microarrray analysis to identify mbs1-regulated genes in C. neoformans. A majority of them were found to be involved in cell cycle regulation and DNA repair. Therefore, this study provides a novel antifungal therapeutic method for treatment of cryptococcosis. total RNAs are extracted 2 strains from H99 (H99 Wild type strain (Cryptococcus neoformans var. grubii serotype A), mbs1Δ), We use the mixed all of total RNAs from this experiment as a control RNA. We use Cy5 as Sample dye and Cy3 as a control dye.
2011-06-23 | E-GEOD-30156 | biostudies-arrayexpress
Project description:Ubiquitination is a reversible protein modification involved in various cellular processes in eukaryotic cells. Deubiquitinating enzymes, the proteins responsible for the removal of ubiquitin, act as essential regulators to maintain ubiquitin homeostasis and to exquisitely regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily within the immunocompromised population. In order to understand the possible influence deubiquitinating enzymes have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of 7 putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5∆ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 appears to be the major deubiquitinating enzyme in C. neoformans for maintaining a pool of free ubiquitin for stress responses, supports the evolutionary divergence of Cryptococcus sp. from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. In addition, other putative deubiquitinase mutants (doa4∆ and ubp13∆) exhibit similar phenotypes to the ubp5∆ mutant, illustrating possible functional overlap among deubiquitinating enzymes in C. neoformans. Certain functioning deubiquitinating enzymes are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host.
2012-04-11 | GSE35067 | GEO
Project description:Ubiquitination is a reversible protein modification involved in various cellular processes in eukaryotic cells. Deubiquitinating enzymes, the proteins responsible for the removal of ubiquitin, act as essential regulators to maintain ubiquitin homeostasis and to exquisitely regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily within the immunocompromised population. In order to understand the possible influence deubiquitinating enzymes have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of 7 putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5∆ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 appears to be the major deubiquitinating enzyme in C. neoformans for maintaining a pool of free ubiquitin for stress responses, supports the evolutionary divergence of Cryptococcus sp. from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. In addition, other putative deubiquitinase mutants (doa4∆ and ubp13∆) exhibit similar phenotypes to the ubp5∆ mutant, illustrating possible functional overlap among deubiquitinating enzymes in C. neoformans. Certain functioning deubiquitinating enzymes are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host.
2012-04-11 | GSE36183 | GEO
Project description:Ubiquitination is a reversible protein modification involved in various cellular processes in eukaryotic cells. Deubiquitinating enzymes, the proteins responsible for the removal of ubiquitin, act as essential regulators to maintain ubiquitin homeostasis and to exquisitely regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily within the immunocompromised population. In order to understand the possible influence deubiquitinating enzymes have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of 7 putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5∆ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 appears to be the major deubiquitinating enzyme in C. neoformans for maintaining a pool of free ubiquitin for stress responses, supports the evolutionary divergence of Cryptococcus sp. from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. In addition, other putative deubiquitinase mutants (doa4∆ and ubp13∆) exhibit similar phenotypes to the ubp5∆ mutant, illustrating possible functional overlap among deubiquitinating enzymes in C. neoformans. Certain functioning deubiquitinating enzymes are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host.
2012-04-11 | GSE36182 | GEO
Project description:Ubiquitination is a reversible protein modification involved in various cellular processes in eukaryotic cells. Deubiquitinating enzymes, the proteins responsible for the removal of ubiquitin, act as essential regulators to maintain ubiquitin homeostasis and to exquisitely regulate protein degradation via the ubiquitination pathway. Cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily within the immunocompromised population. In order to understand the possible influence deubiquitinating enzymes have on growth and virulence of the model pathogenic yeast Cryptococcus neoformans, we generated deletion mutants of 7 putative deubiquitinase genes. Compared to other deubiquitinating enzyme mutants, a ubp5∆ mutant exhibited severely attenuated virulence and many distinct phenotypes, including decreased capsule formation, hypomelanization, defective sporulation, and elevated sensitivity to several external stressors (such as high temperature, oxidative and nitrosative stresses, high salts, and antifungal agents). Ubp5 appears to be the major deubiquitinating enzyme in C. neoformans for maintaining a pool of free ubiquitin for stress responses, supports the evolutionary divergence of Cryptococcus sp. from the model yeast S. cerevisiae, and provides an important paradigm for understanding the potential role of deubiquitination in virulence by other pathogenic fungi. In addition, other putative deubiquitinase mutants (doa4∆ and ubp13∆) exhibit similar phenotypes to the ubp5∆ mutant, illustrating possible functional overlap among deubiquitinating enzymes in C. neoformans. Certain functioning deubiquitinating enzymes are essential for the virulence composite of C. neoformans and provide an additional yeast survival and propagation advantage in the host.
2012-04-11 | GSE36181 | GEO
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
Project description:A family of APSES transcription factor is known to be fungal-specific transcriptional regulators and play important roles in governing growth, differentiation, and virulence of diverse fungal pathogens. Yet none of APSES-like transcription factors have been identified and investigated in a basidiomycetous fungal pathogen, Cryptococcus neoformans. In the present study we discovered an APSES-like transcription factor, Msa1 (Mbp1/Swi4-like APSES protein 1), as one of novel flucytosine-responsive genes (total 194 genes) identified through comparative transcriptome analysis of C. neoformans hybrid sensor kinase mutants, tco1 and tco2 mutants, which displayed differential flucytosine-susceptibility. Supporting the microarray data, Northern blot and quantitative RT-PCR analysis confirmed that expression of MSA1 is rapidly induced in response to flucytosine in the wild-type strain, but not in the tco1 and tco2 mutants. Furthermore, C. neoformans with deletion of the MSA1 gene exhibited increased susceptibility to flucytosine. Intriguingly, Msa1 plays pleiotropic roles in diverse cellular process of C. neoformans. Msa1 positively regulates ergosterol biosynthesis and thereby its inhibition confers increased susceptibility and resistance to amphotericin B and azole drugs, respectively. Msa1 is also involved in DNA damage repair counteracting genotoxic stresses. During sexual differentiation Msa1 represses pheromone production, but promotes cell-cell fusion. Furthermore Msa1 is required for production of antioxidant melanin pigment and full virulence of C. neoformans. Finally we also performed DNA microarrray analysis to identify Msa1-regulated genes in C. neoformans. A majority of them were found to be involved in cell cycle regulation and DNA repair. Therefore, this study provides a novel antifungal therapeutic method for treatment of cryptococcosis. There are more than 95% of genome homology between JEC21 and H99. Therefore 24 slides of JEC21 (cryptococcus neoformans var. neoformans serotype D) 70-mer oligo are used in this analysis, 3 biological replicate experiments are performed, total RNAs are extracted under 2 conditions (with or without treatment of Flucytosine) with 4 strains from H99 (H99 Wild type strain (Cryptococcus neoformans var. grubii serotype A), tco1Δ , tco2Δ , skn7Δ), We use the mixed all of total RNAs from this experiment as a control RNA. We use Cy5 as Sample dye and Cy3 as a control dye.
2011-06-23 | E-GEOD-30154 | biostudies-arrayexpress