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E-MTAB-5309

ABSTRACT: RNA sequencing of the treatment of Aspergillus fumigatus with the new antifungal drug 089 -SYBARIS

PROVIDER: E-MTAB-5309 | ExpressionAtlas | 2019-01-09

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-MTAB-5309-analysis-methods.tsv	Tabular
	E-MTAB-5309-analytics.tsv	Tabular
	E-MTAB-5309-atlasExperimentSummary.Rdata	Rdata
	E-MTAB-5309-configuration.xml	Xml
	E-MTAB-5309-g2_g1-mvaPlot.png	Other

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RNA sequencing of the treatment of Aspergillus fumigatus with the new antifungal drug 089 -SYBARIS

Project description:The mechanism of action of the new antifungal compound 089 was identified in Saccharomyces cerevisiae. The compound had antifungal effects also on pathogenic fungi. While on Candida species the treatment induced cells death, on A. fumigatus strains it inhibited the conidia transition to hyphae. We carried out RNA sequencing analysis to evaluate at the molecular level the effect of the treatment on Aspergillus.

2020-03-04 | E-MTAB-5309 | biostudies-arrayexpress

RNA sequencing of the treatment of Aspergillus fumigatus with the new antifungal drug 089 -SYBARIS

Project description:RNA sequencing of the treatment of Aspergillus fumigatus with the new antifungal drug 089 -SYBARIS

| PRJEB18479 | ENA

Effect of amphotericin B on Aspergillus fumigatus

Project description:Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by genomic approaches. Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by microarray and proteomic methods. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours Experiment was performed in dye swap manner from two different biological replicates

2010-05-26 | E-GEOD-10505 | biostudies-arrayexpress

Effect of amphotericin B on Aspergillus fumigatus

2008-02-14 | GSE10505 | GEO

RNA-Seq of Aspergillus fumigatus mutants resistant to itraconazole, SYBARIS project.

Project description:Two mutant strains of Aspergillus fumigatus derived from strain A1160, HapB and 29.9, display resistance to the antifungal drug itraconazole. To understand what underlying transcriptional processes contribute to this resistance, A1160, HapB and 29.9 were cultured either in the presence or absence of itraconazole. RNA-sequencing was used to compare transcription profiles of each mutant strain with or without the drug, to A1160 with or without drug.

2016-04-30 | E-SYBR-5 | biostudies-arrayexpress

tRNA hypomodification facilitates 5-fluorocytosine resistance via cross-pathway control system activation in Aspergillus fumigatus.

Project description:Increasing antifungal drug resistance is a major concern associated with human fungal pathogens like Aspergillus fumigatus. Genetic mutation and epimutation mechanisms clearly drive resistance, yet the epitranscriptome remains relatively untested. Here, deletion of the A. fumigatus tRNA-modifying isopentenyl transferase ortholog, Mod5, led to altered stress response and unexpected resistance against the antifungal drug 5-fluorocytosine (5-FC). After confirming the canonical isopentenylation activity of Mod5 by LC-MS/MS and Nano-tRNAseq, we performed simultaneous profiling of transcriptomes and proteomes to reveal a comparable overall response to 5-FC stress; however, a premature activation of cross-pathway control (CPC) genes in the knockout was further increased after antifungal treatment. We identified several orthologues of the A. nidulans Major Facilitator Superfamily (MFS) transporter nmeA as specific CPC-client genes in A. fumigatus. Overexpression of Mod5-target tRNATyrGΨA in the ∆mod5 strain rescued select phenotypes but failed to reverse 5-FC resistance, whereas deletion of nmeA largely, but incompletely, reverted the resistance phenotype, implying additional relevant exporters. In conclusion, 5-FC resistance in the absence of Mod5 and i6A likely originates from multifaceted transcriptional and translational changes that skew the fungus towards premature CPC-dependent activation of antifungal toxic-intermediate exporter nmeA, offering a potential mechanism reliant on RNA modification to facilitate transient antifungal resistance.

2024-10-16 | GSE276346 | GEO

Barcode sequencing of Saccharomyces cerevisiae deletion libraries, SYBARIS project

Project description:A systematic approach allowing the identification of the molecular way-of-action of novel potential drugs represents the golden-tool for drug-discovery. While high-throughput screening technologies of large libraries is now well established, the assessment of the drug targets and mechanism of action is still under development. Taking advantage of the yeast model Saccharomyces cerevisiae, we herein applied BarSeq, a Next Generation Sequencing-based method to the analysis of both haploinsufficiency and homozygous fitness effects of a novel antifungal drug ('089') compared to the well-known antifungal ketoconazole. '089' was a novel compound identified in during a screen for antifungal drugs, as it was showing fungicidal effects, and able to affect the yeast fitness at the mitochondrial level (Stefanini et al., 2010. (Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants;.J Biol Chem, 285: 23477-23485.) Integrative bioinformatic analysis of BarSeq, whole genome expression analysis and classical biological assays identified the target and cell pathways affected by the novel antifungal. Confirmation of the effects observed in the yeast model and in pathogenic fungi further demonstrated the reliability of the multi-sided approach and the novelty of the targets and way-of-action of the new class of molecules studied representing a valuable source of novel antifungals.

2016-04-30 | E-SYBR-6 | biostudies-arrayexpress

Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin

Project description:The transcription factor CrzA influences cell wall organization in the pathogenic fungus Aspergillus fumigatus, and also binds to the promoter regions of chitin synthase genes upon exposure to the antifungal drug caspofungin. To gain an overview of the genes directly regulated by CrzA, the CrzA binding sites were determined genome-wide by ChIP-seq

2021-08-02 | GSE179132 | GEO

Aftpo3 and Afdur3, the Aspergillus fumigatus Plasma Membrane Transporters of Polyamines, Regulate Polyamine Homeostasis and Itraconazole Susceptibility

Project description:<p>Aspergillus fumigatus is a notorious opportunistic pathogen that causes Invasive Aspergillosis (IA) infections with high mortality in immunosuppressed individuals. Long-term antifungal drug azole abuse in clinical treatment and agriculture renders it ineffectual or drug resistant. Drug resistance can relate to the cellular metabolites and corresponding gene transcription. In this study, through untargeted metabolomics and transcriptomics following itraconazole (ITC) treatment we identified two plasma membrane-localized polyamine transporters Aftpo3 and Afdur3, which were important for polyamine homeostasis and ITC susceptibility in A. fumigatus. In the absence of Aftpo3 or Afdur3, the levels of cytoplasm polyamines had a moderate increase, accompanied by resistance to ITC. In comparison, overexpression of Aftpo3 or Afdur3 induced drastic increase of polyamines, which were linked with the sensitivity to ITC. Accordingly, our study demonstrated that concentration-dependence of polyamines affected susceptibility of A. fumigatus to ITC, by scavenging reactive oxygen species (ROS) at a moderate concentration or generating ROS at a high concentration rather than drug transport.</p>

2020-12-21 | MTBLS1739 | MetaboLights

Effect of Artemisinin on Aspergillus fumigatus gene expression program

Project description:We examined the antifungal activity of artemisinin against Aspergillus fumigatus (A. fumigatus), a pathogenic filamentous fungus responsible for allergic and invasive aspergillosis in humans and analyzed transcript profiles of the fungus on exposure to Artemisinin. A. fumigatus spores were cultured for 48 h and then treated with artemisinin (at MIC50 concentration) or solvent control (DMSO) for 3 h to study its transcriptomic profiles.

2011-05-11 | GSE21297 | GEO

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