Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597331 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10759814_1.fastq.gz | Fastqsanger.gz | |||
| SRR10759814_2.fastq.gz | Fastqsanger.gz | |||
| SRR10759815_1.fastq.gz | Fastqsanger.gz | |||
| SRR10759815_2.fastq.gz | Fastqsanger.gz | |||
| SRR10759816_1.fastq.gz | Fastqsanger.gz |
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Project description:Here we show that the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance and the other via an epigenetic RNA interference (RNAi)-mediated pathway that results in unstable drug resistance. The peptidyl-prolyl isomerase FKBP12 interacts with FK506 to form a complex that inhibits the protein phosphatase calcineurin. In M. circinelloides, inhibition of calcineurin by FK506 blocks the transition to hyphae and enforces yeast growth. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance, restoring hyphal growth in the presence of this drug. In parallel, RNAi is spontaneously triggered to silence the FKBP12 fkbA gene, giving rise to drug-resistant epimutants. FK506-resistant epimutants readily reverted to the drug-sensitive wild type (WT) phenotype when selection was released by growth without drug. High-throughput small RNA (sRNA) sequencing showed abundant sRNA antisense to fkbA only in the epimutants and not in the WT or revertant strains. Analysis of RNAi mutants revealed components required for the establishment of drug resistant epimutants as well as other factors that constrain or reverse the epimutation pathway. Silencing involves generation of a double stranded RNA trigger intermediate using the fkbA mature mRNA as template. These results uncover a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi regulatory mechanisms in fungi and other eukaryotes.
2014-07-22 | GSE56353 | GEO
Project description:Mucor species belongs to the Mucorales order within the phylum Mucoromycota, an early diverging fungal lineage. The purpose of this study was to investigate at the transcriptome scale the similarities and differences that could be linked to different lifestyles. Five strains pertaining to five species were studied: M. fuscus and M. lanceolatus, two species used in cheese ripening, M. racemosus, a recurrent cheese spoiler sometimes described as an opportunistic pathogen, M. circinelloides, often described as an opportunistic pathogen and M. endophyticus, a plant endophyte species.
2018-09-01 | E-MTAB-6453 | biostudies-arrayexpress
Project description:Mucorales are basal fungi that opportunistically cause a fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic organisms. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.
2024-03-20 | GSE233894 | GEO
Project description:We sequenced Endogenous short RNAs in Mucor circinelloides fungus grown in standard liquid culture. Short RNAs were profiled in wild type, Dicer-like 1 mutant (dcl1-), Dicer-like 2 mutant (dcl2-) and double Dicer mutant (dcl1-/dcl2-) strains. We identified many loci that produced less short RNAs in the dcl2- strain suggesting that DCL2 is the major protein generating short RNAs in Mucor circinelloides. Endogenous short RNAs were profiled in wild type, single and double dcl mutant strains.
2010-04-28 | E-GEOD-18958 | biostudies-arrayexpress
Project description:We sequenced Endogenous short RNAs in Mucor circinelloides fungus grown in standard liquid culture. Short RNAs were profiled in wild type, Dicer-like 1 mutant (dcl1-), Dicer-like 2 mutant (dcl2-) and double Dicer mutant (dcl1-/dcl2-) strains. We identified many loci that produced less short RNAs in the dcl2- strain suggesting that DCL2 is the major protein generating short RNAs in Mucor circinelloides.
2010-04-28 | GSE18958 | GEO
Project description:ChIP-seq experiment with two outer kinetochore proteins to identify the centromeric sequences of Mucor circinelloides
2019-10-09 | GSE132687 | GEO
Project description:Transcriptional profiling of wild-type strain (R7B) of the fungus Mucor circinelloides comparing control mycelia grown for 18 hours in the dark with mycelia grown in the same conditions and illuminated with white light for 20 min. Goal was to identify genes regulated by a pulse of white light.
2016-06-06 | GSE58264 | GEO
Project description:Calcineurin/NFAT signaling pathway has been shown to play important roles in various tissues such as the immune system, cardiac muscle and neuron. Although recent studies have shown that the pathway is involved in the regulation of hair growth, the precise mechanism is still unclear. In this study, we examine the molecular mechanism which is regulated by calcineurin/NFAT pathway, using two specific inhibitors for the pathway. Transcriptional profiling of human keratinocyte cell line, PHK cells, comparing control untreated PHK cells with cyclosporin A (CsA)-treated or 11R-VIVIT-treated PHK cells. Goal was to identify the effects of NFAT inhibitors on PHK cell proliferation. Cyclosporine A is a chemical compound, which strongly inhibits calcineurin phosphatase activity cooperating with cyclophilin, resulting in inhibition of NFAT signaling pathway. 11R-VIVIT is a cell-permeable peptide, which specifically interacts with NFAT and inhibits its binding to calcineurin, resulting in competitive inhibition of NFAT signaling pathway. Three-condition experiment; untreated PHK cells, CsA-treated PHK cells and 11R-VIVIT-treated PHK cells. Supplementary files: Significantly up-regulated genes across 4 different comparisons.
2010-11-08 | E-GEOD-25175 | biostudies-arrayexpress
Project description:Novel pathogenic Mucorales identified using the silkworm infection model
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Project description:Mucor circinelloides f. circinelloides NRRL 3614 Resequencing
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