Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE80474
PROVIDER: PRJNA319029 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3405790.fastq.gz | Fastqsanger.gz | |||
| SRR3405800.fastq.gz | Fastqsanger.gz | |||
| SRR3405810.fastq.gz | Fastqsanger.gz | |||
| SRR3405820.fastq.gz | Fastqsanger.gz | |||
| SRR3405830.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Cell-cycle transcript dynamics from two species of wild-type budding yeast growing at 30 degrees Celsius in rich media: Saccharomyces cerevisiae (BF264-15D background) and Cryptococcus neoformans var. grubii (H99F background). We compared programs of cell-cycle-regulated genes between distantly related budding yeasts.
2016-12-07 | GSE80474 | GEO
Project description:The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation.
| S-EPMC5137879 | biostudies-literature
Project description:Cryptococcus spp. are environmental fungi that first must adapt to the host environment before they can cause life-threatening meningitis in immunocompromised patients. Host CO2 concentrations are 100-fold higher than the external environment and strains unable to grow at host CO2 concentrations are not pathogenic. Using a genetic screening and transcriptional profiling approach, we found that the TOR pathway is critical for C. neoformans adaptation to host CO2 partly through Ypk1-dependent remodeling of phosphatidylserine asymmetry at the plasma membrane. We also identified a C. neoformans ABC/PDR transporter (PDR9) that is highly expressed in CO2-sensitive environmental strains, suppresses CO2-induced phosphatidylserine remodeling, and increases susceptibility to host concentrations of CO2. Interestingly, regulation of plasma membrane lipid asymmetry by the TOR-Ypk1 axis is distinct in C. neoformans compared to S. cerevisiae. Finally, host CO2 concentrations suppress the C. neoformans pathways that respond to host temperature (Mpk1) and pH (Rim101), indicating that host adaptation requires a stringent balance among distinct stress responses.
2023-10-24 | GSE241788 | GEO
Project description:The target of rapamycin (TOR) pathway is an evolutionarily conserved signal transduction system that is activated by varying nutrient and environmental signals and governs a plethora of eukaryotic biological processes, but its role in Cryptococcus neoformans remains elusive. In this study, we investigated the TOR pathway by functionally characterizing two Tor-like kinases, Tor1 and Tlk1, in C. neoformans. We successfully deleted TLK1, but not TOR1. TLK1 deletion did not result in any evident in vitro phenotypes, suggesting that Tlk1 is mainly dispensable for the growth of C. neoformans. We further demonstrated that Tor1, but not Tlk1, is essential and the target of rapamycin by constructing and analyzing conditionally regulated strains and sporulation analysis of heterozygous mutants in the diploid strain background. To analyze the functions of Tor1 in more detail, we constructed constitutive TOR1 overexpression strains. Tor1 negatively regulated thermotolerance and the DNA damage response, which are two important virulence factors of C. neoformans. We also found that TOR1 overexpression reduced Mpk1 phosphorylation, which is required for cell wall integrity and thermoresistance, and Rad53 phosphorylation, which governs the DNA damage response pathway. Tor1 is localized to the cytoplasm but enriched in the vacuole membrane. Phosphoproteomics and transcriptomics revealed that Tor1 regulates a variety of biological processes, including metabolic processes, cytoskeleton organization, ribosome biogenesis, autophagy, and stress response. TOR inhibition by rapamycin caused actin depolarization in a Tor1-dependent manner. Finally, screening rapamycin-sensitive and -resistant kinase and transcription factor mutants revealed that the TOR pathway may crosstalk with a number of signaling pathways, including the Hog1 pathway. In conclusion, our study demonstrates that a single Tor1 kinase plays a variety of roles in the fungal meningitis pathogen C. neoformans.
2019-04-03 | GSE129227 | GEO
Project description:Cryptococcus neoformans is a type of pathogenic fungi that can cause infections in people with weakened immune systems. This fungal pathogen can survive in the body by growing at the host's body temperature (37\'b0C), forming a carbohydrate capsule, and producing melanin. When Cryptococcus neoformans strains lack certain septin proteins, they cannot grow at 37\'b0C and are not able to cause infections in mice. However, it is not yet clear how septins help the yeast to grow at the host's body temperature. Septins are a group of proteins that are important for cell division and morphogenesis. In the model organism, Saccharomyces cerevisiae septins are essential. S. cerevisiae septins form a higher-order complex at the mother bud-neck to scaffold over 80 proteins, including those involved in cell wall organization, cell polarity, and cell cycle control. In C. neoformans, septins also form a complex at the mother bud neck but the septin interacting proteome in this species remains largely unknown. In this study, the entire septin complex in C. neoformans was uncovered as downregulated during the stationary growth phase and heat stress. In addition, we investigated the septin interactome in C. neoformans, shedding light on the proteins that interact with septins Cdc3 and Cdc10 under ambient temperature and heat stress, respectively. Our findings unveiled a diverse array of interacting proteins, including components of Golgi to plasma membrane transport, cell division, and single-stranded DNA binding. \'a0Overall, this study delineates septins in C. neoformans as part of the cytoskeleton and cytoskeleton-dependent cytokinesis and provides a landscape of septin interactors to investigate and further understand septin biology in fungal systems.
2024-10-28 | PXD052407 | Pride
Project description:Cryptococcus neoformans interactions with murine macrophages are critical for disease. In this project we analyzed fungal proteins which were co-purified with murine host proteins after interaction. H99 C. neoformans was opsonized with mAb 18B7 and addedd to murine macrophages. Then murine cells were lysed and cell extracts submitted to proteomics.
2023-03-11 | PXD024951 | Pride
Project description:Purpose: Defining the regulatory role of the transcription factor Sre1 in C. neoformans. Methods: Chromatin immunoprecipitation followed by high-throughput sequencing was performed using chromatin immunoprecipitated DNA from the strain Flag-Sre1 grown in low- and high-iron media under normoxia and hypoxia condition. Results: Sre1 directly bind to the promoter region of the genes involved in ergosterol biosynthetic pathway and iron acquisition in C. neoformans.
2020-09-01 | GSE135038 | GEO
Project description:Purpose: Understanding the regulatory role of Sre1 in Cryptococcus neoformans. Methods: The transcriptome profiles of the wild-type and sre1 mutant were generated by RNA-seq using Illumina Hiseq. The transcriptome profile of the sre1 mutant was compared with that of the wild-type strain. Results: The Sterol Regulatory Element Binding Protein, Sre1 is a major regulator for the genes involved in ergosterol biosynthetic pathway and iron acquisition in C. neoformans.
2020-09-01 | GSE135039 | GEO
Project description:Lysine acetylation is critical in regulating important biological processes in many organisms, yet little is known about acetylome evolution and its contribution to phenotypic diversity. Here, we compare the acetylomes of baker’s yeast and the three deadliest human fungal pathogens, Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus. Using mass spectrometry enriched for acetylated peptides together with public data from Saccharomyces cerevisiae, we show that fungal acetylomes are characterized by dramatic evolutionary dynamics and limited conservation in core biological processes. Notably, the levels of protein acetylation in pathogenic fungi correlate with their pathogenicity. Using gene knockouts and pathogenity assays in mice, we identify deacetylases with critical roles in virulence and protein translation elongation. Finally, through mutational analysis of deactylation motifs we find evidence of positive selection at specific acetylation motifs in fungal pathogens. These results shed new light on the pathogenicity regulation mechanisms underlying the evolution of fungal acetylomes.
2019-04-26 | GSE116040 | GEO
Project description:Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperature, and is essential for stress adaptation and virulence. The transcription factor Crz1 is a major calcineurin effector in Saccharomyces cerevisiae and other fungi. Calcineurin dephosphorylates Crz1, thereby enabling Crz1 nuclear translocation and transcription of target genes. Here we show that Crz1 is dephosphorylated by calcineurin, and crz1Δ mutants display phenotypes intermediate between wild-type and calcineurin mutants. RNA-sequencing revealed 102 genes that are regulated in a calcineurin/Crz1-dependent manner at 37°C. 99 genes were down-regulated in cna1Δ and crz1Δ mutants, indicating these genes are normally activated by the calcineurin/Crz1 pathway at high temperature. About 58% of calcineurin-Crz1 target genes have unknown functions, while genes with known or predicted functions are involved in cell wall remodeling, calcium transport, and pheromone production. Surprisingly, only five genes have orthologs known to be calcineurin/Crz1-dependent in S. cerevisiae. 393 genes are independently regulated by calcineurin, and Crz1 regulates 59 genes independently of calcineurin. Taken together, these results indicate that the calcineurin/Crz1-dependent pathway controls a transcriptional circuit that has been extensively rewired in C. neoformans compared to S. cerevisiae. Given the intermediate crz1Δ mutant phenotype, and our recent evidence for a calcineurin regulatory network impacting mRNA in P-bodies and stress granules independently of Crz1, calcineurin likely acts on factors beyond Crz1 that govern mRNA expression/stability to operate a branched transcriptional/post-transcriptional stress response network necessary for fungal virulence. Taken together, our findings reveal the core calcineurin-Crz1 stress response cascade is maintained from ascomycetes to a pathogenic basidiomycete fungus, but its output has been extensively rewired to promote fungal virulence.
2017-04-07 | GSE93005 | GEO