Unravelling of the novel melanin biosynthesis-signalling networks in Cryptococcus neoformans
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ABSTRACT:
PROVIDER: PRJNA545271 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9141550_1.fastq.gz | Fastqsanger.gz | |||
| SRR9141550_2.fastq.gz | Fastqsanger.gz | |||
| SRR9141560_1.fastq.gz | Fastqsanger.gz | |||
| SRR9141560_2.fastq.gz | Fastqsanger.gz | |||
| SRR9141570_1.fastq.gz | Fastqsanger.gz |
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Project description:Melanin is an antioxidant polyphenol pigment, which is required for the pathogenicity of many human and plant fungal pathogens. Nevertheless, its comprehensive regulatory mechanism still remain elusive. In this study, we systematically analyzed melanin-regulating signaling pathways in Cryptococcus neoformans. Here we identified four core melanin-regulating TFs, Bzp4, Usv101, Mbs1, and Hob1, which are required for induction of the laccase gene (LAC1). Bzp4, Usv101 and Mbs1 independently regulate LAC1 induction while Hob1 controls Bzp4 and Usv101 expression. Both Bzp4 and Usv101 are translocated from the cytoplasm into the nucleus upon nutrient starved condition, while Mbs1 is constitutively localized in the nucleus. Notably, the cAMP pathway is not involved in regulation of the four TFs, while the HOG pathway negatively regulates induction of BZP4 and LAC1. As potential kinases upstream of the core TFs, we identified the nine core kinases, whose deletion leads to defective melanin production and LAC1 induction. Deletion of GSK3 or KIC1 abolishes induction of LAC1 and BZP4, and also perturbs nuclear translocation of Bzp4. Notably, Gsk3 also regulates the expression of HOB1, USV101, and MBS1, indicating that it is a critical melanin-regulating kinase. Finally, the RNA-sequencing based transcriptome analysis of the wild-type and bzp4Δ, usv101Δ, hob1Δ, and mbs1Δ strains under nutrient rich and starved conditions reveals that the core melanin-regulating TFs govern redundant and distinct classes of genes, which are involved in a variety of biological processes.
2019-05-30 | GSE131891 | GEO
Project description:Influence of copy number changes at several chromosomes to melanin production and virulence of Cryptococcus neoformans
2011-04-19 | GSE28673 | GEO
Project description:Influence of copy number changes at several chromosomes to melanin production and virulence of Cryptococcus neoformans Black(B4) and white(W2) strains were compared to each other. Black variant from white strain (W2BA1) is also compared to the black strain(B4).
2011-04-19 | E-GEOD-28673 | biostudies-arrayexpress
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
Project description:Thermotolerance, a key factor essential for the virulence of pathogenic fungi including Cryptococcus neoformans, remains largely unexplored in terms of its underlying mechanism. In this study, our findings demonstrate that Set3C, a widely distributed and conserved histone deacetylase complex, is required for thermotolerance in Cryptococcus neoformans. Specifically, the deletion of the core subunit Set302, responsible for the integrity of the complex, results in a significant reduction in the growth ability under high stress and the viability at extreme temperature. Moreover, the absence of Set302 leads to a decrease in the production of capsule and melanin. Transcriptomics analysis revealed that Set302 regulates a large number of genes compared to normal condition, and their expression is responsive to heat stress. Notably, we observed that Set302 positively influences the expression of genes related to ubiquitin-proteasome system (UPS) at high temperature. Using GFP-α-synuclein overexpression model, we observed a pronounced accumulation of misfolded proteins under heat stress, consequently inhibiting the thermotolerance of Cryptococcus neoformans. Furthermore, the loss of Set302 exacerbates this inhibition of thermotolerance. Interestingly, set302∆ strain exhibits a similar phenotype under proteasome stress as it does under high temperature. We also found that set302∆ strain displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings indicate that Set302 modulates the degradation of misfolded proteins through the UPS pathway, thereby affecting the thermotolerance and pathogenicity of Cryptococcus neoformans.
2023-09-05 | GSE242109 | GEO
Project description:The RNA interference (RNAi) mediated by homology-dependent degradation of the target mRNA with small RNA molecules plays a key role in controlling transcription and translation processes in a number of eukaryotic organisms. The RNAi machinery is also evolutionarily conserved in a wide variety of fungal species, including pathogenic fungi. To elucidate the physiological functions of the RNAi pathway in Cryptococcus neoformans that causes fungal meningitis, here we performed genetic analyses for genes encoding Argonaute (AGO1 and AGO2), RdRP (RDP1), and Dicers (DCR1 and DCR2) in both serotype A and D C. neoformans. The present study shows that Ago1, Rdp1, and Dcr2 are the major components of the RNAi process occurring in C. neoformans. However, the RNAi machinery is not involved in regulation of production of two virulence factors (capsule and melanin), sexual differentiation, and diverse stress response. To further gain insights into the global regulatory circuit governed by the RNAi pathway, comparative transcriptome analysis using the serotype A and D RNAi mutants was performed. Notably, an increase in transcript abundance of active transposons, such as T2 and T3, was observed in the rdp1? mutant. Therefore, this study can improve our understanding of the role of the RNAi genes in human fungal pathogens including C. neoformans. This SuperSeries is composed of the following subset Series: GSE21176: Molecular and Functional Characterization of the role of RNA silencing components in Cryptococcus neoformans [RNAi_Serotype A] GSE21177: Molecular and Functional Characterization of the role of RNA silencing components in Cryptococcus neoformans [RNAi_Serotype D] Refer to individual Series
2010-05-01 | E-GEOD-21178 | biostudies-arrayexpress
Project description:WD40 motif-containing Msi1-like (MSIL) proteins play pleiotropic cellular functions as a negative regulator of the Ras/cAMP-pathways and a component of chromatin assembly factor-I (CAF-I), and yet have not been studied in fungal pathogens. Here we identified and characterized an MSIL protein, Msl1, in Cryptococcus neoformans, which can cause fatal meningoencephalitis in humans. Notably, Msl1 was not a functional ortholog for the yeast Msi1 but played pleiotropic roles in C. neoformans in both cAMP-dependent and -independent manners but mainly Ras-independently. Msl1 negatively controlled antioxidant melanin production and sexual differentiation, which can be repressed by inhibiting the cAMP-signaling pathways. In contrast, Msl1 controlled thermotolerance, diverse stress responses, and antifungal drugs resistance in Ras/cAMP-independent manners. Cac2, which is the second CAF-I component, appeared to play both redundant and distinct function with Msl1. Msl1 is required for full virulence of C. neoformans. Transcriptome and proteomic analysis identified a group of Msl1-regulated genes or -interacting proteins, respectively, which mostly include stress-related genes, including HSP12, HSP78, SSA1, SSA4, and STM1. Furthermore, we identified the third putative component of CAF-1, Rlf2, in C. neoformans. In conclusion, this study demonstrated the pleiotropic roles of Msl1 in human fungal pathogen C. neoformans, providing a novel antifungal therapeutic target. There is more than 95% genome homology between JEC21 and H99. Therefore, 6 slides of JEC21 (Cryptococcus neoformans var. neoformans serotype D) 70-mer oligos are used in this analysis. Total RNAs are extracted from 2 strains from H99 (H99 wild-type strain (Cryptococcus neoformans var. grubii serotype A), msl1M-NM-^T). 3 biological replicate experiments are performed for each strain. We use the mix of all total RNAs from this experiment as the control RNA. We use Cy3 as the test sample dye and Cy5 as the control dye.
2012-08-23 | E-GEOD-40303 | biostudies-arrayexpress
Project description:Unravelling the pathobiological role of the fungal KEOPS complex in Cryptococcus neoformans
| PRJNA859376 | ENA
Project description:Cryptococcus neoformans is an opportunistic, human fungal pathogen which undergoes fascinating switches in cell cycle control and ploidy when it encounters stressful environments such as the human lung. Here we carry out a mechanistic analysis of the spindle checkpoint which regulates the metaphase to anaphase transition, focusing on Mps1 kinase and the downstream checkpoint components Mad1 and Mad2. We demonstrate that Cryptococcus mad1D or mad2D strains are unable to respond to microtubule perturbations, continuing to re-bud and divide, and die as a consequence. Fluorescent tagging of Chromosome 3, using a lacO array and mNeonGreen-lacI fusion protein, demonstrates that mad mutants are unable to maintain sister-chromatid cohesion in the absence of microtubule polymers. Thus, the classic checkpoint functions of the SAC are conserved in Cryptococcus. In interphase, GFP-Mad1 is enriched at the nuclear periphery, and it is recruited to unattached kinetochores in mitosis. Purification of GFP-Mad1 followed by mass spectrometric analysis of associated proteins show that it forms a complex with Mad2 and that it interacts with other checkpoint signalling components (Bub1) and effectors (Cdc20 and APC/C sub-units) in mitosis. We also demonstrate that overexpression of Mps1 kinase is sufficient to arrest Cryptococcus cells in mitosis, and show that this arrest is dependent on both Mad1 and Mad2. We find that a C-terminal fragment of Mad1 is an effective in vitro substrate for Mps1 kinase and map several Mad1 phosphorylation sites. Some sites are highly conserved within the C-terminal Mad1 structure and we demonstrate that mutation of threonine 667 (T667A) leads to loss of checkpoint signalling and abrogation of the GAL-MPS1 arrest. Thus Mps1-dependent phosphorylation of C-terminal Mad1 residues is a critical step in Cryptococcus spindle checkpoint signalling. We conclude that CnMps1 protein kinase, Mad1 and Mad2 proteins have all conserved their important, spindle checkpoint signalling roles helping ensure high fidelity chromosome segregation.
2024-05-27 | PXD052327 | 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