Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MRNA-seq of Aspergillus fumigatus RNAi double knockouts

ABSTRACT: 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.

ORGANISM(S): Aspergillus fumigatus

PROVIDER: GSE223618 | GEO | 2023/02/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Functional characterization of the RNA interference pathway in A. fumigatus reveals its potential for antifungal therapy

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 growth 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 first investigated the genetic variation in RNAi-associated genes in a large collection of environmental and clinical genomes, where we found that RNAi is evolutionarily conserved even in clinical strains. Using endogenously expressed inverted-repeat transgenes complementary to both a conditionally essential gene and a nonessential gene, we determined that a subset of the RNAi componentry is active in inverted-repeat transgene silencing in conidia and mycelium. A multi-condition mRNA-seq analysis linked the A. fumigatus dicer-like enzymes and RNA-dependent RNA polymerases to regulation of conidial ribosome biogenesis genes; however, surprisingly few endogenous small RNAs were identified in conidia that could explain this broad change. Although RNAi was not clearly linked to growth or stress response defects in the RNAi knockouts, serial passaging of RNAi knockout strains for six generations resulted in lineages with diminished spore production over time, indicating that loss of RNAi can exert a fitness cost on the fungus. 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.

2023-02-17 | PXD039739 | Pride

sRNA-seq of Aspergillus fumigatus RNAi double knockouts

2024-05-25 | GSE267454 | GEO

sRNA-seq of Aspergillus fumigatus RNAi double knockouts

Project description:sRNA-seq of Aspergillus fumigatus RNAi double knockouts

| PRJNA1111541 | ENA

mRNA-seq of Aspergillus fumigatus RNAi double knockouts

Project description:mRNA-seq of Aspergillus fumigatus RNAi double knockouts

| PRJNA926981 | ENA

Exploitation of the RNA interference pathway of the human fungal pathogen Aspergillus fumigatus

Project description:RNA-based therapeutics are an emerging class of drugs that are changing the way we treat infectious diseases. The versatility of this class is clearly on display in the rapid design and adaptation of the mRNA vaccines to SARS-CoV-2. Despite the success of these therapeutics against viruses, research into RNA-based therapeutics against human fungal pathogens, a major source of human morbidity and mortality, is lacking. Here, we provide proof-of-principle that RNA-based therapeutics hold potential against human fungal pathogens like Aspergillus fumigatus. We provide an improved mechanistic description of the RNA interference pathway of this important human pathogen by describing the genetic variation in RNAi-related genes using a large collection of environmental and clinical genomes, the proteins regulated by the system using advanced proteomics analysis, and the RNAi components essential for hairpin-induced silencing. We then exploit this pathway using a heterologously expressed hairpin RNA construct to silence the pabA gene of A. fumigatus to inhibit growth. The data presented here provide a foundation for a mechanistic description of novel RNA regulatory pathways in A. fumigatus and provide a first step towards the development of RNA-based therapeutics against this important human fungal pathogen.

2023-02-01 | PXD033984 | Pride

RNA-Seq analysis of gene expression changes by wildtype and Nlrx1 deficient BEAS-2B airway epithelial cells in response to A. fumigatus viable conidia

Project description:Aspergillus fumigatus is an opportunistic fungal pathogen of the respiratory system that may cause invasive infection or an allergic response. Bronchial airway epithelial cells compromise the most abundant cell type of the pulmonary-air interface. Our recent findings suggest loss of Nlrx1 by BEAS-2B airway epithelial cells result in a hyper inflammatory response as well as decreased conidial processing. We challenged wildtype Nlrx1 deficient BEAS-2B cells with viable A. fumigatus AF293 conidia to identify early response differentially expressed genes and pathways between the two cell populations.

2023-01-20 | GSE144652 | GEO

A phylogenetic approach to explore the Aspergillus fumigatus conidial surfome and its role in pathogenesis

Project description:Aspergillus fumigatus is the most important pulmonary fungal pathogen and is able to cause several diseases collectively called aspergillosis. Conidia is the most important infection structure making the initial contact with the human host. Here, we used a phylogenomic approach comparing proteins present in the A. fumigatus conidial surface, two closely related non-pathogenic species A. fischeri and A. oerlinghausenensis, and the far-related pathogenic A. lentulus. We were able to identify 62 proteins specifically expressed on A. fumigatus conidial surface. We deleted 42 of the encoding-genes and observed that many of them have altered susceptibility to macrophage killing, penetration and damage to epithelial cells, and cytokine production. We demonstrated that one of these genes encoding a glycosylasparaginase is modulating IL-1β levels and is important for the infection in an immunocompetent murine model. Our results provide opportunities for characterizing A. fumigatus effectors important for evasion and modulation of the immune response.

2024-06-26 | PXD044190 | Pride

Functional genomics of Aspergillus fumigatus conidiospores interacting with human bronchial epithelial cells

Project description:The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to conidiospores of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. This exposure is asymptomatic in most individuals but can be associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidiospores in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the 16HBE cell line and a transgenic A. fumigatus strain expressing green fluorescent protein. The transcriptional profiles of A. fumigatus conidiospores incubated in the presence or absence of human cells were compared, revealing significant changes in fungal gene expression in response to conidial interaction with cells.

2011-06-01 | GSE16630 | GEO

Functional genomics of Aspergillus fumigatus conidiospores interacting with human bronchial epithelial cells

2011-06-01 | E-GEOD-16630 | biostudies-arrayexpress

A phylogenomic approach to explore the Aspergillus fumigatus conidia surforme and its role in pathogenesis

Project description:Aspergillus fumigatus is the most important pulmonary fungal pathogen. Virulence has evolved several times in the section Aspergillii. However, there are species in this section, such as A. fischerii and A. oerlinghausensis, that are very closely related to A. fumigatus but are not reported as pathogens. By using trypsin shaving, we have identified the proteins on the conidial surface of conidia and swollen conidia of A. fumigatus, A. fischeri, A. oerlinghausensis, and A. lentulus. We have identified about 900 proteins in all four species and shown 52 that are unique in A. fumigatus. Both A. fischerii and A. oerlinghausensis have homologues for most of these proteins. However, they are not expressed in the conidia and and could reflect specific A. fumigatus traits important for infection and/or immune evasion.

2024-06-26 | PXD031199 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data