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Aspergillus fumigatus

ABSTRACT: Network Modelling using Transcription Sequence Data Reveals Novel MAPK Interactions Important for Drug Resistance

PROVIDER: PRJNA240892 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1186420.fastq.gz	Fastqsanger.gz
	SRR1186430.fastq.gz	Fastqsanger.gz
	SRR1186440.fastq.gz	Fastqsanger.gz
	SRR1186450.fastq.gz	Fastqsanger.gz
	SRR1186421.fastq.gz	Fastqsanger.gz

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Aspergillus fumigatus

Project description:Drug resistance in Aspergillus fumigatus

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The role of Aspergillus fumigatus SmiA transcription factor in the miltefosine resistance

Project description:By searching for new drugs against fungal pathogens, we found that miltefosine is active against Aspergillus fumigatus clinical isolates. A library of transcription factors (TF) null mutants was then challenged with this drug and we discovered a novel TF that confers resistance to miltefonise, named here SmiA. By using ChIP-seq, we searched for SmiA targets upon miltefosine treatment.

2021-08-23 | GSE178664 | 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.

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sRNA-seq of Aspergillus fumigatus RNAi double knockouts

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Methylation array profiling of DIPG tumours, patient-derived cell culture, and patient-derived xenografts from the BIOMEDE phase II prospective trial

Project description:BIOMEDE (NCT02233049) was a phase II, biopsy-driven clinical trial in DIPG patients with randomisation of stratification between dasatinib, erlotinib and everolimus. Methylation array profiling was carried out alongside drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. Alongside exome, RNAseq, phospho-proteomics, these data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatment

2020-08-31 | E-MTAB-9282 | biostudies-arrayexpress

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>

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Aspergillus fumigatus

Project description:Whole Genome Mutational Profiling of Drug Resistant A. fumigatus Strains

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Project description:Genomic Surveillance of Drug-Resistant Aspergillus fumigatus in Yunnan Greenhouses

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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.

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Project description:The RNA interference (RNAi) pathway has evolved numerous functionalities in eukaryotes, with many on display in Kingdom Fungi. RNAi can regulate gene expression, facilitate drug resistance, or even be altogether lost to improve virulence potential in some fungal pathogens. In the WHO fungal priority pathogen, Aspergillus fumigatus, the RNAi system is known to be intact and functional. To extend our limited understanding of A. fumigatus RNAi, we performed a multi-condition mRNA-seq analysis comparing expression of several RNAi double knockout mutants with the wild-type strain in conidia and mycelium grown for 24 or 48 hours. The analysis linked the A. fumigatus dicer-like enzymes and RNA-dependent RNA polymerases to regulation of conidial ribosome biogenesis. Cumulatively, A. fumigatus RNAi appears to play an active role in defense against double-stranded RNA species alongside a previously unappreciated housekeeping function in regulation of conidial ribosomal biogenesis genes.

2023-02-14 | GSE223618 | GEO

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