Conserved and specific responses to hypoxia in Aspergillus oryzae and Aspergillus nidulans determined by comparative transcriptomics

Abstract

Hypoxia imposes stress on filamentous fungi that require oxygen to proliferate. Global transcription analysis of Aspergillus oryzae grown under hypoxic conditions found that the expression of about 50% of 4,244 affected genes was either induced or repressed more than 2-fold. A comparison of these genes with the hypoxically regulated genes of Aspergillus nidulans based on their predicted amino acid sequences classified them as bi-directional best hit (BBH), one-way best hit (extra homolog, EH), and no-hit (non-syntenic genes, NSG) genes. Clustering analysis of the BBH genes indicated that A. oryzae and A. nidulans down-regulated global translation and transcription under hypoxic conditions, respectively. Under hypoxic conditions, both fungi up-regulated genes for alcohol fermentation and the γ-aminobutyrate shunt of the tricarboxylate cycle, whereas A. oryzae up-regulated the glyoxylate pathway, indicating that both fungi eliminate NADH accumulation under hypoxic conditions. The A. oryzae NS genes included specific genes for secondary and nitric oxide metabolism under hypoxic conditions. This comparative transcriptomic analysis discovered common and strain-specific responses to hypoxia in hypoxic Aspergillus species.

Identification of Hypoxia-Inducible Target Genes of Aspergillus fumigatus by Transcriptome Analysis Reveals Cellular Respiration as an Important Contributor to Hypoxic Survival

“…The induction of the glyoxylate cycle may help to avoid NADH accumulation by bypassing two NADH-producing steps of the TCA cycle. The increased levels of transcripts contributing to amino acid transport are consistent with results from A. nidulans (18) and may point to increased production of specific amino acids under hypoxia. In a previous study, we characterized the adaptation of A. fumigatus to hypoxia in a batch fermenter within a time window of 2 to 24 h (defined here as short-term response).…”

“…Many similarities in the adaptation to hypoxia can be found when comparing our results with those from previous studies of Aspergillus species. As observed for A. nidulans and A. oryzae (18,20), intracellular trafficking processes and cytoskeletal transcripts were downregulated under hypoxic conditions, most probably in order to reduce ATP consumption. In contrast, genes participating in the glyoxylate pathway were upregulated under hypoxic conditions, whereas the regulation of glycolytic genes was heterogenous (see Data Set S1 in the supplemental material).…”

“…Alternatively, the reduction of fumarate to succinate is linked with the regeneration of NAD ϩ and may function as an electron sink, as described for Mycobacterium tuberculosis (63). Also, the fungal species Aspergillus niger, A. oryzae, and S. cerevisae produce elevated amounts of succinate under oxygen-limiting conditions (18,52,64). Gene expression of the cytosolic fumarate reductase frdA was significantly induced in A. fumigatus during hypoxia, and succinate was detectable in the supernatant of hypoxic batch cultures.…”

“…In contrast, genes participating in the glyoxylate pathway were upregulated under hypoxic conditions, whereas the regulation of glycolytic genes was heterogenous (see Data Set S1 in the supplemental material). In this aspect, the hypoxic response of A. fumigatus resembles that of A. oryzae (18). The induction of the glyoxylate cycle may help to avoid NADH accumulation by bypassing two NADH-producing steps of the TCA cycle.…”

“…Several examples of such alternative electron sinks have already been described in diverse fungal species. In Aspergillus oryzae and Aspergillus nidulans, genes involved in ethanol fermentation are induced during hypoxic growth conditions (18). However, for A. fumigatus no growth phenotype was observed under oxygen-limiting conditions for strains devoid of ethanol fermentation (19).…”