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NosA, a transcription factor important in Aspergillus fumigatus stress and developmental response, rescues the germination defect of a laeA deletion.

ABSTRACT: Aspergillus fumigatus is an increasingly serious pathogen of immunocompromised patients, causing the often fatal disease invasive aspergillosis (IA). One A. fumigatus virulence determinant of IA is LaeA, a conserved virulence factor in pathogenic fungi. To further understand the role of LaeA in IA, the expression profile of ?laeA was compared to wild type, and several transcription factors were found significantly misregulated by LaeA loss. One of the transcription factors up-regulated over 4-fold in the ?laeA strain was Afu4g09710, similar in sequence to Aspergillus nidulans NosA, which is involved in sexual development. Here we assessed loss of nosA (?nosA) and overexpression of nosA (OE::nosA) on A. fumigatus in both a wild type and ?laeA background. Based on the multiple alterations of physiological development of single and double mutants, we suggest that NosA mediates the decreased radial growth and delayed conidial germination observed in ?laeA strains, the former in a light dependent manner. The ?nosA mutant showed increased virulence in the Galleria mellonella larvae model of disseminated aspergillosis, potentially due to its increased growth and germination rate. Furthermore, the A. fumigatus nosA allele was able to partially remediate sexual development in an A. nidulans ?nosA background. Likewise, the A. nidulans nosA allele was able to restore the menadione sensitivity defect of the A. fumigatus ?nosA strain, suggesting conservation of function of the NosA protein in these two species.

SUBMITTER: Soukup AA

PROVIDER: S-EPMC3483426 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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NosA, a transcription factor important in Aspergillus fumigatus stress and developmental response, rescues the germination defect of a laeA deletion.

Soukup Alexandra A AA Farnoodian Mitra M Berthier Erwin E Keller Nancy P NP

Fungal genetics and biology : FG & B 20120925 11

Aspergillus fumigatus is an increasingly serious pathogen of immunocompromised patients, causing the often fatal disease invasive aspergillosis (IA). One A. fumigatus virulence determinant of IA is LaeA, a conserved virulence factor in pathogenic fungi. To further understand the role of LaeA in IA, the expression profile of ΔlaeA was compared to wild type, and several transcription factors were found significantly misregulated by LaeA loss. One of the transcription factors up-regulated over 4-fo ...[more]

PMID: 23022264

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Project description:Biosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. In Aspergillus molds, asexual development is regulated by the BrlA > AbaA > WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of ΔbrlA, ΔabaA, and ΔwetA mutant and wild-type strains of the human pathogen Aspergillus fumigatus. We find that BrlA, in addition to regulating production of developmental SMs, regulates vegetative SMs and the SrbA-regulated hypoxia stress response in a concordant fashion to LaeA. We further show that the transcriptional and metabolic equivalence of the ΔbrlA and ΔlaeA mutations is mediated by an LaeA requirement preventing heterochromatic marks in the brlA promoter. These results provide a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this pathogen. IMPORTANCE Filamentous fungi produce a spectacular variety of small molecules, commonly known as secondary or specialized metabolites (SMs), which are critical to their ecologies and lifestyles (e.g., penicillin, cyclosporine, and aflatoxin). Elucidation of the regulatory network that governs SM production is a major question of both fundamental and applied research relevance. To shed light on the relationship between regulation of development and regulation of secondary metabolism in filamentous fungi, we performed global transcriptomic and metabolomic analyses on mutant and wild-type strains of the human pathogen Aspergillus fumigatus under conditions previously shown to induce the production of both vegetative growth-specific and asexual development-specific SMs. We find that the gene brlA, previously known as a master regulator of asexual development, is also a master regulator of secondary metabolism and other cellular processes. We further show that brlA regulation of SM is mediated by laeA, one of the master regulators of SM, providing a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this pathogen.

Dataset Information

NosA, a transcription factor important in Aspergillus fumigatus stress and developmental response, rescues the germination defect of a laeA deletion.

Publications

NosA, a transcription factor important in Aspergillus fumigatus stress and developmental response, rescues the germination defect of a laeA deletion.

Similar Datasets

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