Glucose is a widely used carbon source in laboratory practice to culture Aspergillus fumigatus, however, glucose availability is often low in its “natural habitats”, including the human body. We used a physiological–transcriptomical approach to reveal differences between A. fumigatus Af293 cultures incubated on glucose, glucose and peptone, peptone (carbon limitation), or without any carbon source (carbon starvation). Autolytic cell wall degradation was upregulated by both carbon starvation and limitation. The importance of autolytic cell wall degradation in the adaptation to carbon stress was also highlighted by approximately 12.4% of the A. fumigatus genomes harboring duplication of genes involved in N-acetyl glucosamine utilization. Glucose withdrawal increased redox imbalance, altered both the transcription of antioxidative enzyme genes and oxidative stress tolerance, and downregulated iron acquisition, but upregulated heme protein genes. Transcriptional activity of the Gliotoxin cluster was low in all experiments, while the Fumagillin cluster showed substantial activity both on glucose and under carbon starvation, and the Hexadehydro-astechrome cluster only on glucose. We concluded that glucose withdrawal substantially modified the physiology of A. fumigatus, including processes that contribute to virulence. This may explain the challenge of predicting the in vivo behavior of A. fumigatus based on data from glucose rich cultures.
Glutathione (GSH) is an abundant tripeptide that plays a crucial role in shielding cellular macromolecules from various reactive oxygen and nitrogen species in fungi. Understanding GSH metabolism is of vital importance to deciphering redox regulation in these microorganisms. In the present study, to better understand the GSH metabolism in filamentous fungi, we investigate functions of the dugB and dugC genes in the model fungus Aspergillus nidulans. These genes are orthologues of dug2-3 involved in cytosolic GSH degradation in the yeast. The deletion (Δ) of dugB, dugC, or both resulted in a moderate increase in the GSH content in the mycelia grown on glucose, reduced conidia production, and disturbed sexual development. In agreement with these observations, transcriptome data showed that genes encoding MAP kinase pathway elements (e.g. steC, sskB, hogA, mkkA) or regulatory proteins of conidiogenesis and sexual differentiation (e.g. flbA,C,E, nosA, rosA, nsdC,D) were down-regulated in the ΔdugBΔdugC mutant. Deletion of dugB and/or dugC slowed down the depletion of GSH pools under carbon starvation. It also reduced accumulation of reactive oxygen species, decreased autolytic cell wall degradation and enzyme secretion but increased sterigmatocystin formation. Transcriptome data demonstrated that enzyme secretions - in contrast to mycotoxin production - were controlled at post-transcriptional level. We suggest that GSH connects starvation and redox regulation to each other: Cells utilize GSH as stored carbon source during starvation. The reduction of GSH content alters the redox state activating regulatory pathways responsible for carbon starvation stress responses. Importance Glutathione (GSH) is a widely distributed tripeptide in both eukaryotes and prokaryotes. Owing to its very low redox potential, antioxidative character and high intracellular concentration, GSH profoundly shapes the redox status of cells. Our observations suggest that GSH metabolism and/or the redox status of cells plays a determinative role in several important aspects of fungal life, including oxidative stress defense, protein secretion, secondary metabolite production (including mycotoxin formation) as well as sexual and asexual differentiations. We demonstrated that even a slightly elevated GSH level can substantially disturb the homeostasis of fungi. This information could be important for development of new GSH producing strains or for any biotechnologically relevant processes where the GSH content, antioxidant capacity or oxidative stress tolerance of a fungal strain is manipulated.
Cadmium is an exceptionally toxic industrial and environmental pollutant classified as a human carcinogen. In order to provide insight into how we can keep our environment safe from cadmium contamination and prevent the accumulation of it in the food chain, we aim to elucidate how Aspergillus nidulans, one of the most abundant fungi in soil, survives and handles cadmium stress. As AtfA is the main transcription factor governing stress responses in A. nidulans, we examined genome-wide expression responses of wild-type and the atfA null mutant exposed to CdCl2. Both strains showed up-regulation of the crpA Cu2+/Cd2+ pump gene and AN7729 predicted to encode a putative bis(glutathionato)-cadmium transporter, and transcriptional changes associated with elevated intracellular Cys availability leading to the efficient adaptation to Cd2+. Although the deletion of atfA did not alter the cadmium tolerance of the fungus, the cadmium stress response of the mutant differed from that of a reference strain. Promoter and transcriptional analyses of the “Phospho-relay response regulator” genes suggest that the AtfA-dependent regulation of these genes can be relevant in this phenomenon. We concluded that the regulatory network of A. nidulans has a high flexibility allowing the fungus to adapt efficiently to stress both in the presence and absence of this important transcription factor.
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