Aspergillus nidulans dynamic transcriptome during synchronized conidiation
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ABSTRACT:
ORGANISM(S): Aspergillus nidulans
PROVIDER: GSE281842 | GEO | 2024/11/18
REPOSITORIES: GEO
Similar Datasets
Project description:In filamentous fungi, secondary metabolism is often linked with developmental processes such as conidiation. In this study we analyzed the link between secondary metabolism and conidiation in the main industrial producer of the β-lactam antibiotic penicillin, the ascomycete Penicillium chrysogenum. Therefore, we generated mutants defective in two central regulators of conidiation, the transcription factors BrlA and StuA, respectively. Inactivation of both BrlA and StuA blocked conidiation and altered hyphal morphology during growth on solid media, as shown by light and scanning electron microscopy, but did not affect biomass production during liquid submerged growth. Genome-wide transcriptional profiling identified a complex StuA- and BrlA-dependent regulatory network, including genes previously shown to be involved in development and secondary metabolism. Remarkably, inactivation of StuA, but not BrlA, drastically down-regulated expression of the penicillin biosynthetic gene cluster during solid and liquid submerged growth. In agreement, penicillin V production was wild type-like in BrlA-deficient strains but 99 % decreased in StuA-deficient strains during liquid submerged growth as shown by HPLC analysis. Thus, among identified regulators of penicillin V production StuA has the most severe influence. Over-expression of StuA increased the transcript levels of BrlA and AbaA (another developmental regulator), de-repressed conidiation during liquid submerged growth, but did not affect penicillin V productivity. Taken together, these data demonstrate an intimate but not exclusive link between regulation of development and secondary metabolism in P. chrysogenum. Transcriptomes of PcbrlA- and PcstuA- deletion mutants were compared with expression data from recipient strain deltaPcku70 as a control Mycelia from the transformants and the reference strain were harvested at successive stages of development for RNA extraction and hybridization on Affymetrix microarrays.
2011-01-04 | E-GEOD-23326 | biostudies-arrayexpress
Project description:Inhalation of conidia of the opportunistic mold Aspergillus fumigatus by immunocompromised hosts can lead to invasive pulmonary disease. Inhaled conidia that escape immune defenses germinate to form filamentous hyphae that invade lung tissues. Conidiation rarely occurs during invasive infection of the human host, allowing the bulk of fungal energy to be directed towards vegetative growth. We hypothesized that forced induction of conidiation during infection can suppress A. fumigatus vegetative growth, impairing the ability of this organism to cause disease. To study the effects of conidiation pathway dysregulation on A. fumigatus virulence, a key transcriptional regulator of conidiation (brlA) was expressed under the control of a doxycycline-inducible promoter. Time- and dose-dependent brlA overexpression was observed in response to doxycycline both in vitro and in vivo. Exposure of the inducible brlA overexpression strain to low doses of doxycycline under vegetative growth conditions in vitro induced conidiation, while high doses arrested growth. Overexpression of brlA attenuated A. fumigatus virulence in both an invertebrate and mouse model of invasive aspergillosis. RNA sequencing studies and phenotypic analysis revealed that brlA-overexpression results in altered cell signaling, amino acid and carbohydrate metabolism, including a marked up-regulation of trehalose biosynthesis and a downregulation in the biosynthesis of the polysaccharide virulence factor galactosaminogalactan. This proof-of-concept study demonstrates that activation of the conidiation pathway in A. fumigatus can reduce virulence and suggests that brlA-inducing small molecules may hold promise as a new class of therapeutics for A. fumigatus infection.
2020-01-15 | GSE143601 | GEO
Project description:Beauveria bassiana abaA (BbabaA) and brlA (BbbrlA) regulating genes involved in conidiation
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Project description:In filamentous fungi, secondary metabolism is often linked with developmental processes such as conidiation. In this study we analyzed the link between secondary metabolism and conidiation in the main industrial producer of the β-lactam antibiotic penicillin, the ascomycete Penicillium chrysogenum. Therefore, we generated mutants defective in two central regulators of conidiation, the transcription factors BrlA and StuA, respectively. Inactivation of both BrlA and StuA blocked conidiation and altered hyphal morphology during growth on solid media, as shown by light and scanning electron microscopy, but did not affect biomass production during liquid submerged growth. Genome-wide transcriptional profiling identified a complex StuA- and BrlA-dependent regulatory network, including genes previously shown to be involved in development and secondary metabolism. Remarkably, inactivation of StuA, but not BrlA, drastically down-regulated expression of the penicillin biosynthetic gene cluster during solid and liquid submerged growth. In agreement, penicillin V production was wild type-like in BrlA-deficient strains but 99 % decreased in StuA-deficient strains during liquid submerged growth as shown by HPLC analysis. Thus, among identified regulators of penicillin V production StuA has the most severe influence. Over-expression of StuA increased the transcript levels of BrlA and AbaA (another developmental regulator), de-repressed conidiation during liquid submerged growth, but did not affect penicillin V productivity. Taken together, these data demonstrate an intimate but not exclusive link between regulation of development and secondary metabolism in P. chrysogenum. Transcriptomes of PcbrlA- and PcstuA- deletion mutants were compared with expression data from recipient strain deltaPcku70 as a control
2011-01-04 | GSE23326 | GEO
Project description:Aspergillus nidulans dynamic transcriptome during synchronized conidiation
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Project description:Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug resistance in this pathogen. Exposure of C. glabrata cells to micafungin (an echinocandin) leads to the isolation of a mutant exhibiting resistance to echinocandin and azole antifungals. The drug-resistant phenotype is due to a non-synonymous mutation (R70H) in gene IPI1, which is known to be involved in pre-rRNA processing in Saccharomyces cerevisiae. Azole resistance in the ipi1-R70H mutant depends on the Pdr1 transcription factor, which regulates the expression of multidrug transporters. We show that the C. glabrata Ipi1 protein physically interacts with the ribosome-related chaperones Ssb and Ssz1, both of which bind to Pdr1. The Ipi1-Ssb/Ssz1 complex inhibits Pdr1-mediated gene expression and multidrug resistance in C. glabrata, in contrast to S. cerevisiae where Ssz1 has been shown to act as a positive regulator of Pdr1. Furthermore, micafungin exposure reduces metabolic activity and cell proliferation in the ipi1-R70H mutant, which may contribute to micafungin tolerance.
2024-12-19 | GSE255839 | GEO
Project description:Linking cell reproduction and survival is a key task of all life forms. All fungi in the genus Aspergillus reproduce by forming asexual spores called conidia, of which formation is governed by the central regulatory circuit, BrlA->AbaA->WetA. Here, we report that WetA is a key multi-functional regulator that bridged spore differentiation, long-term survival, and chemical development in Aspergillus flavus.
2017-06-04 | GSE95711 | GEO
Project description:Asexual development is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In the filamentous fungal genus Aspergillus, the production of asexual spores is primarily governed by the BrlA-AbaA-WetA central regulatory cascade. The final step in this cascade, which is controlled by the WetA protein, not only governs cellular development (i.e., the morphological differentiation of spores) but also ensures its coupling with chemical development (i.e., the coordinated production and deposition of diverse secondary metabolites, such as aflatoxins, into spores). While the wetA gene is conserved across the genus Aspergillus, the structure and degree of conservation of the BrlA-AbaA-WetA regulatory cascade and the broader wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type (WT) asexual spores in three representative species spanning the diversity of the genus Aspergillus: the genetic model A. nidulans, the agricultural pest A. flavus, and the human pathogen A. fumigatus. We discovered that WetA regulates asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade’s first step. Furthermore, ChIP-seq experiments in A. nidulans asexual spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory element, which we term the WetA Response Element (WRE). Interestingly, the WRE is found completely conserved in the non-coding region upstream of the wetA translation start site of many diverse Aspergillus genomes. In contrast, several global transcriptional regulators, most notably those in the velvet complex (veA, velB, and laeA) known to regulate the coupling between asexual development and production of secondary metabolites, show species-specific regulatory patterns. These results suggest that the BrlA-AbaA-WetA cascade’s regulatory role in cellular and chemical development of asexual spores is functionally conserved, but that the WetA-associated GRN has diverged during Aspergillus evolution. This entry is for the RNA-seq data.
2018-07-24 | GSE114143 | GEO
Project description:Asexual development is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In the filamentous fungal genus Aspergillus, the production of asexual spores is primarily governed by the BrlA-AbaA-WetA central regulatory cascade. The final step in this cascade, which is controlled by the WetA protein, not only governs cellular development (i.e., the morphological differentiation of spores) but also ensures its coupling with chemical development (i.e., the coordinated production and deposition of diverse secondary metabolites, such as aflatoxins, into spores). While the wetA gene is conserved across the genus Aspergillus, the structure and degree of conservation of the BrlA-AbaA-WetA regulatory cascade and the broader wetA gene regulatory network (GRN) remain largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type (WT) asexual spores in three representative species spanning the diversity of the genus Aspergillus: the genetic model A. nidulans, the agricultural pest A. flavus, and the human pathogen A. fumigatus. We discovered that WetA regulates asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascade’s first step. Furthermore, ChIP-seq experiments in A. nidulans asexual spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory element, which we term the WetA Response Element (WRE). Interestingly, the WRE is found completely conserved in the non-coding region upstream of the wetA translation start site of many diverse Aspergillus genomes. In contrast, several global transcriptional regulators, most notably those in the velvet complex (veA, velB, and laeA) known to regulate the coupling between asexual development and production of secondary metabolites, show species-specific regulatory patterns. These results suggest that the BrlA-AbaA-WetA cascade’s regulatory role in cellular and chemical development of asexual spores is functionally conserved, but that the WetA-associated GRN has diverged during Aspergillus evolution. This entry is for the ChIP-seq data.
2018-07-24 | GSE114141 | GEO