Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA Seq in wild type and zfs1 deficient C. albicans

ABSTRACT: Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins bind to AU-rich regions in the 3'-untranslated regions (UTR) of target mRNAs, leading to their deadenylation and accelerated decay. Family members in S. cerevisiae influence iron metabolism, whereas the family member in S. pombe leads to defects in cell-cell interactions. In the important human fungal pathogen Candida albicans, deep sequencing of transcripts in mutants deficient in the analogous protein, Zfs1p, revealed 156 transcripts whose levels were significantly increased by at least 1.5-fold. Of these, 113 (72%) contained at least a single predicted TTP family member binding site in their 3’UTR. In contrast, 102 transcripts were significantly down-regulated by 1.5-fold or more, and only 5 (5%) of these contained potential binding sites. Sequences of the proteins encoded by the putative Zfs1p targets were highly conserved among other Candida species, while the predicted Zfs1p binding sites in these mRNAs progressively “disappeared” with increasing evolutionary distance from the parental species. The C. albicans results support the concept that the biochemical functions of the TTP family members in fungal organisms are highly conserved, yet each species appears to have evolved its own set of transcripts that are regulated by this mechanism.

ORGANISM(S): Candida albicans

PROVIDER: GSE53073 | GEO | 2015/12/04

SECONDARY ACCESSION(S): PRJNA230804

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA Seq in wild type and zfs1 deficient C. albicans

Project description:Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins bind to AU-rich regions in the 3'-untranslated regions (UTR) of target mRNAs, leading to their deadenylation and accelerated decay. Family members in S. cerevisiae influence iron metabolism, whereas the family member in S. pombe leads to defects in cell-cell interactions. In the important human fungal pathogen Candida albicans, deep sequencing of transcripts in mutants deficient in the analogous protein, Zfs1p, revealed 156 transcripts whose levels were significantly increased by at least 1.5-fold. Of these, 113 (72%) contained at least a single predicted TTP family member binding site in their 3âUTR. In contrast, 102 transcripts were significantly down-regulated by 1.5-fold or more, and only 5 (5%) of these contained potential binding sites. Sequences of the proteins encoded by the putative Zfs1p targets were highly conserved among other Candida species, while the predicted Zfs1p binding sites in these mRNAs progressively âdisappearedâ with increasing evolutionary distance from the parental species. The C. albicans results support the concept that the biochemical functions of the TTP family members in fungal organisms are highly conserved, yet each species appears to have evolved its own set of transcripts that are regulated by this mechanism. Strains were grown in YPD media to approximately OD600=0.75 and total RNA was harvested from four biological replicates each of WT and 2 independent isolates of the zfs1 deletion.

2015-12-04 | E-GEOD-53073 | biostudies-arrayexpress

in vitro ubiquitination by E3 ligase Cbl-b

Project description:Fungal infections claim an estimated 1.5 million lives every year. Mechanisms that protect from fungal infections are still elusive. Recognition of fungal pathogens relies on C-type lectin receptors (CLR) and their downstream signaling kinase SYK. Here we report that the E3-ubiquitin-ligase CBL-B controls proximal C-type lectin receptor signaling in macrophages and dendritic cells. We show that CBL-B associates with SYK and ubiquitinates SYK, Dectin-1, and Dectin-2 upon fungal recognition. Functionally, CBL-B deficiency results in increased inflammasome activation, enhanced reactive oxygen species production, and increased fungal killing. Genetic deletion of Cblb protects mice from morbidity caused by cutaneous infection and markedly improves survival upon a lethal systemic infection with Candida albicans. Based on these findings, we engineered a cell-permeable CBL-B inhibitory peptide that protects mice from lethal C. albicans infections. We thus describe a key role for Cblb in the regulation of innate anti-fungal immunity and establish a novel paradigm for the treatment of fungal sepsis.

2016-06-17 | PXD004256 | Pride

Filamentation is Associated with Reduced Pathogenicity of Multiple Non-albicans Candida Species

Project description:Candidiasis affects a wide variety of immunocompromised individuals, including HIV/AIDS patients and cancer patients on chemotherapy. Candida albicans, a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non-albicans Candida species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as C. albicans, although definitive evidence is lacking. To address this question, we used strains for two NACS, Candida tropicalis and Candida parapsilosis, that are genetically engineered to constitutively express the key transcriptional regulator UME6 and drive strong filamentation both in vitro and during infection in vivo. Unexpectedly, both strains showed a dramatic reduction in organ fungal burden and clearance of infection in response to UME6 expression. Consistent with these findings, we observed that a C. tropicalis hyperfilamentous mutant was significantly reduced and a filamentation-defective mutant was slightly increased for organ fungal burden. Comprehensive immune profiling did not reveal any significant changes in the host immune response to UME6 expression in the NACS. Interestingly, however, whole-genome transcriptional profiling indicated that while genes important for filamentation were induced by UME6 expression in C. tropicalis and C. parapsilosis, other genes involved in a variety of processes important for pathogenesis were strongly down-regulated. Our findings are significant because they suggest fundamental evolutionary differences in the relationship between morphology and pathogenicity among Candida species and that NACS do not necessarily possess the same virulence properties as C. albicans.

2019-10-01 | GSE134321 | GEO

Differential Gene Expression and mRNA decay in Wild-Type and Myeloid-specific TTP Family Member Triple (M-Triple) Knock-out macrophages using RNA-Seq

Project description:Members of the tristetraprolin (TTP) family of RNA-binding proteins can bind to and promote the decay of specific transcripts containing AU-rich motifs. ZFP36 (TTP) is best known for regulating cytokine expression in myeloid cells; however, the mammalian paralogues ZFP36L1 and ZFP36L2 have not been viewed as important in controlling inflammation. To study potential functional overlaps of these three TTP family proteins in myeloid cells, we developed myeloid-specific knock-out (M-KO) mice of these genes, singly and together. M-Zfp36-KO mice exhibited a mild inflammatory syndrome late in life, while M-Zfp36l1-KO and M-Zfp36l2-KO mice had no apparent spontaneous phenotypes. Mice with simultaneous deficiency of all three TTP family members in myeloid cells developed a severe, spontaneous, inflammatory phenotype, with a median survival of 8 weeks. Macrophages derived from these mice contained many more stabilized transcripts than cells from M-Zfp36-KO mice, many encoding pro-inflammatory cytokines and chemokines. Our findings emphasize the importance of all three family members, acting in concert, in myeloid cell function.

2023-10-20 | GSE229923 | GEO

Differential Gene Expression and mRNA decay in Wild-Type and Myeloid-specific TTP Knock-out macrophages using RNA-Seq

2023-10-20 | GSE229922 | GEO

Functions of the Mediator subunit Med31 in Candida albicans support a role in shaping species-specific gene expression.

Project description:Mediator is an essential, evolutionarily conserved co-regulator of RNA polymerase II. Studies in model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe showed remarkably conserved roles for Mediator despite high species divergence, and thus whether Mediator contributed to establishment of species-specific gene expression programs within related fungal species remains an open question. Here we show that in the fungal pathogen Candida albicans, the Mediator middle domain subunit Med31 has a conserved role with non-pathogenic model yeasts in regulation of Ace2-dependent cytokinesis genes and stress responses, but also additional roles in the transcription of genes associated with virulence traits: genes related to filamentous growth and gene families expanded in pathogenic vs non-pathogenic yeasts, such as the ALS adhesins and the FGR6 family of filamentous growth regulators. Consistently, Med31 is required for two key virulence attributes of C. albicans: filamentous growth and biofilm formation. Unlike our data in C. albicans, no role for Med31 in adhesin expression has been reported in model yeasts. To show biological relevance for the control over adhesin gene expression, we demonstrate that ALS1 is a relevant Med31 target for development of biofilms. Collectively, our data supports a role for Med31 in shaping species-specific gene expression in related fungal species.

2012-02-20 | GSE31632 | GEO

Augmented enterocyte damage during Candida albicans and Proteus mirabilis coinfection

Project description:The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen Candida albicans adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast Candida albicans and the Gram-negative bacterium Proteus mirabilis resulting in enhanced host cell damage. This synergistic effect was conserved across different P. mirabilis isolates and occurred also with non-albicans Candida species and C. albicans mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the P. mirabilis hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between Candida and Proteus is induced by contact, but also by soluble factors. Specifically, we identified Candida-mediated glucose consumption and farnesol production as potential triggers for Proteus virulence. In summary, our study demonstrates that coinfection of enterocytes with C. albicans and P. mirabilis can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification via nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination.

2022-05-09 | PXD031222 | Pride

Genome-wide transcriptional profiling of human PBMCs stimulated with Candida albicans and non-fungal inflammatory stimuli

Project description:Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections, but human anti-fungal immunity remains poorly defined. Expression profiling of Candida-stimulated human peripheral blood mononuclear cells (PBMCs) provides new insights into Candida-specific host defense mechanisms in humans.

2014-05-01 | GSE42606 | GEO

High-throughput RNA Sequencing of BMDM of Mus musculus stimulated by C. auris or C. albicans

Project description:Candida auris has been globally recognized as a multidrug-resistant human fungal pathogen that contributes for the worldwide occurrence of nosocomial outbreaks. It has been reported that C. auris was able to avoid neutrophil attack, suggestive of an impaired innate immune response. Whether C. auris evades the innate immune recognition of BMDM (bone marrow derived macrophage) remains poorly understood, and as for well-known Candida species -C. albicans, it can trigger immune response. To determine whether occurs difference between immune response stimulated by C. auris or C. albicans, we performed mRNA-seq of BMDM stimulated by C. auris or C. albicans.

2022-05-21 | GSE203508 | GEO

Functions of the Mediator subunit Med31 in Candida albicans support a role in shaping species-specific gene expression.

2012-02-20 | E-GEOD-31632 | biostudies-arrayexpress