Characterization of regulators of G protein signaling, rgsD and rax1 of Aspergillus fumigatus
Ontology highlight
ABSTRACT:
ORGANISM(S): Aspergillus fumigatus
PROVIDER: GSE100101 | GEO | 2018/06/16
REPOSITORIES: GEO
Similar Datasets
Project description:Pathogens have to cope with oxidative, iron- and carbon-limitation stresses in the human body. To understand how combined iron-carbon limitation alters oxidative stress response, Aspergillus fumigatus was cultured in glucose-peptone or peptone containing media supplemented or not with deferiprone as iron chelator. Changes in the transcriptome in these cultures were recorded after H2O2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes only the cat2 catalase-peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless to culturing conditions in oxidative stress protection, while enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g. iron availability, or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy.
2024-04-03 | GSE256524 | GEO
Project description:The outer layers of the fungal cell wall are the first barrier facing external challenges. In theinvasive morphotype of the airborne pathogen Aspergillus fumigatus, i.e. conidia, the outer cell wall consists of α-(1,3)-glucan, melanin and proteinaceous rodlets made up by the RodA hydrophobin. The hydrophobicity of the RodA rodlets facilitates air dispersal of conidia and progression within lungs. When conidia reach the alveolae, these are phagocytosed by host cells and killed upon germination, which requires melanin and rodlets elimination to occur. The dormant condition of the conidia protects them against activation of the host killing pathways. The outer cell wall of conidia is thus essential for maintaining the viability of the fungus. To study the role of α-(1,3)-glucan, melanin, and RodA rodlets in conidia protection, multiple mutants without two or the three major components of the outer layer were constructed and analyzed. Deletions led to the exposure of new molecules on the conidial surface. Multiple gene deletions did not always lead to logical additivity of the phenotypes. Unexpected compensatory cell wall surface modifications were indeed observed, such as the synthesis of the mycelial virulence factor galactosaminogalactan, the presence of chitin and glycoproteins or specific changes in permeability. In spite of significant modifications, sensitivity to killing by phagocytic host cells of the multiple mutants involving melanin changed little compared to the sensitive parent strain lacking melanin (ΔpksP), further indicating the importance of melanin in protecting conidia against killing by monocytes.
2019-01-30 | PXD011734 | Pride
Project description:Aspergillus fumigatus transcriptome analysis of the asexual developmental stage in atfA deletion mutant
| PRJDB3180 | ENA
Project description:Sexual reproduction of the human pathogen Aspergillus fumigatus (teleomorph: Neosartorya fumigata) was assumed to be absent or cryptic until recently, when fertile crosses among geographically restricted environmental isolates were described. Here, we provide evidence for mating, fruiting body development, and ascosporogenesis accompanied by genetic recombination between unrelated, clinical isolates of A. fumigatus, and this evidence demonstrates the generality and reproducibility of this long-time-undisclosed phase in the life cycle of this heterothallic fungus. Successful mating requires the presence of both mating-type idiomorphs MAT1-1 and MAT1-2, as does expression of genes encoding factors presumably involved in this process. Moreover, analysis of an A. fumigatus mutant deleted for the nsdD gene suggests a role of this conserved regulator of cleistothecium development in hyphal fusion and hence heterokaryon formation.
| S-EPMC2863953 | biostudies-literature
Project description:Infection by the human pathogenic fungus Aspergillus fumigatus is initialized by the outgrowth of asexual spores (conidia) into the lung tissue of the immunocompromised host following an inhalation of the airborne conidia. The resident phagocytes, the alveolar macrophages are the first immune cells to encounter invading conidia. However, A. fumigatus conidia employ versatile mechanisms to evade the host immune defense and establish a severe invasive infection. Previously, we showed that depending on the presence of conidial 1,8-dihydroxynaphthalene (DHN) melanin, A. fumigatus circumvents intracellular killing by manipulating the phagolysosomal maturation process. Here, by comparative dual proteomics we analyzed proteins of phagolysosomes containing melanized wild-type or non-melanized pksP mutant conidia. Bioinformatics compiled a regulatory module of differentially abundant proteins that mirrors processes targeted by the fungus for immune evasion. Those are i.e. vATPAse-driven phagolysosomal acidification, endocytic trafficking, signal transduction, energy metabolism and immune response. In detail, we found alterations of vATPase complex assembly and impaired abundances of mTOR and MAPK signaling molecules, Rab5 and Vamp8 mediators of endosomal trafficking as well as Lamp1 and cathepsin Z lysosomal markers.
2018-03-08 | PXD006134 | Pride
Project description:Genome-wide transcriptional changes under oxidative stress in iron-starved Aspergillus fumigatus cultures
| PRJNA374516 | ENA
Project description:The isolation and properties of a group of alcohols from the mycelium of Aspergillus fumigatus Fresenius are described. Mass-, nuclear-magnetic-resonance- and infrared-spectrometric studies coupled with evidence from ozonolytic degradation and chromatography show the mixture to contain hexahydroprenols-18, -19, -20, -21, -22, -23 and -24. Each contains a saturated ;hydroxy-terminal' isoprene residue, a saturated omega-terminal isoprene residue and a saturated zeta-isoprene residue (adjacent to the omega-residue). The presence of only two trans-isoprene residues is also a feature of the series of alcohols, but the precise position of these in each molecule is not known.
| S-EPMC1270265 | biostudies-other
Project description:In the last few years, increasing numbers of viruses infecting fungi have been identified. In this study, we used an in silico approach for the analysis of deep RNA sequencing data in order to discover and characterize putative genomic ssRNA or dsRNA mycovirus sequences in Aspergillus fumigatus. RNA sequencing reads of A. fumigatus strains were mapped against the A. fumigatus Af293 reference genome. Unmapped reads were collected for de novo assembly. Contigs were analyzed by Blastx comparison with a mycovirus protein database. Assembled viral genomes were used as template for remapping of RNA sequencing reads. In total, deep RNA sequencing results from 11 A. fumigatus strains were analyzed for the presence of mycoviral genomic RNAs. In 9 out of 11 strains, putative mycoviral RNA genomes were identified. Three strains were infected with two different mycovirus species. Two strains were infected with Aspergillus fumigatus polymycovirus type-1 (AfuPmV-1). Four strains contained fully recovered genomic RNA of unknown narna-like viruses designated as Aspergillus fumigatus narnavirus-1 and Aspergillus fumigatus narnavirus-2 (AfuNV-1 and AfuNV-2). Both viruses showed 38% amino acid sequence identity to Beihai narna-like virus-21. Three strains contained partially recovered genomic RNA of an unknown narna-like virus. Two strains contained fully recovered genomic RNAs of an unknown partitivirus designated as Aspergillus fumigatus partitivirus-2 (AfuPV-2) which showed 50% amino acid sequence identity to Alternaria alternata partitivirus-1. Finally, one strain contained fully recovered genomic RNA of an unknown mitovirus designated as Aspergillus fumigatus mitovirus-1 (AfuMV-1) which showed 34% amino acid sequence identity to Sclerotina sclerotiorum mitovirus. In silico analysis of deep RNA sequencing results showed that a majority of the A. fumigatus strains used here were infected with mycoviruses. Four novel A. fumigatus RNA mycoviruses could be identified: two different Aspergillus fumigatus narna-like viruses, one Aspergillus fumigatus partitivirus, and one Aspergillus fumigatus mitovirus.
| S-EPMC6059430 | biostudies-literature
Project description:Transcriptome in response to heat, superoxide, and osmotic stresses in Aspergillus fumigatus mycelia
| PRJDB6203 | ENA
Project description:Neutrophil-derived extracellular vesicles have regained scientific interest as potent ‘wireless’ modulators with pleiotropic effects on the immune system. A few studies have addressed their role in the context of microbial pathogenesis showing their bacteriostatic effects against Staphylococcus aureus in vitro and their potential as diagnostic markers in the onset of bacterimic sepsis in vivo. Here, we provided first insights into the vesicle release driven by the clinically relevant pathogenic fungus Aspergillus fumigatus that causes invasive infections in immunocompromised individuals worldwide often with a lethal outcome. Neutrophils, stimulated with fungal spores, potently produced vesicles that we refer as anti-fungal extracellular vesicles (afEVs). We revealed that the conidial surface pigment of A. fumigatus dihydroxynaphthalene (DHN) melanin - a well known fungal virulence factor - is a key ‘switch-on/off’ governing vesicle production. We profiled the kinetics of afEV formation and showed that DHN-melanin interferes with the vesicle number, vesicle surface maturation markers such as CD11b, CD63 and CD177 and governs the enrichment of distinct afEV subpopulations unrelated to apoptosis. Simultaneously we tracked down the fate of neutrophils during afEV formation and observed mulivesicular body formation that led to active export of CD11b, CD63 and CD177 by shedding from the surface of neutrophils onto the surface afEVs. By dissecting the proteome cargo of afEVs produced against wild-type and melanin-free conidia we verified that DHN-melanin also manipulates the type of cargo neutrophils accumulate in the vesicles upon confronting conidia with different cell wall integrity. afEVs contained higher amounts of antimicrobial peptides than spontaneously released EVs from uninfected neutrophils. Last but not least afEVs exhibit fungistatic effects and also modulate cell wall morphogenesis of hyphae.
2019-05-17 | PXD005994 | Pride