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Abstract Under synchronized conidiation, over 2500 gene products show differential expression, including transcripts for bothbrlAandabaA, which increase steadily over time. In contrast, during wall-stress induced by the echinocandin micafungin, thebrlAtranscript is upregulated while theabaAtranscript is not. In addition, whenmpkA(last protein kinase in the cell wall integrity signaling pathway) is deleted,brlAexpression is not upregulated in response to wall stress. Together, these data imply BrlA may play a role in a cellular stress-response which is independent of the canonical BrlA-mediated conidiation pathway. To test this hypothesis, we performed a genome-wide search and found 332 genes with a putative BrlA response element (BRE) in their promoter region. From this set, we identified 28 genes which were differentially expressed in response to wall-stress, but not during synchronized conidiation. This set included seven gene products whose homologues are involved in transmembrane transport and 14 likely to be involved in secondary metabolite biosynthesis. We selected six of these genes for further examination and find that they all show altered expression behavior in thebrlAdeletion strain. Together, these data support the idea that BrlA plays a role in various biological processes outside asexual development. ImportanceTheAspergillus nidulanstranscription factor BrlA is widely accepted as a master regulator of conidiation. Here, we show that in addition to this function BrlA appears to play a role in responding to cell-wall stress. We note that this has not been observed outsideA. nidulans. Further, BrlA-mediated conidiation is highly conserved acrossAspergillusspecies, so this new functionality is likely relevant in otherAspergilli. We identified several transmembrane transporters that have altered transcriptional responses to cell-wall stress in abrlAdeletion mutant. Based on our observation, together with what is known about thebrlAgene locus’ regulation, we identifybrlAβas the likely intermediary in function ofbrlAin the response to cell-wall stress.
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This content will become publicly available on March 3, 2026
Synthetic Generation of Dynamic Omics Data Demonstrates Aspergillus nidulans BrlA Paradoxical Wall Stress Response
Abstract We propose a method to generate additional dynamic omics trajectories which could support pathway analysis methods such as enrichment analysis, genetic programming, and machine learning. Using long short-term memory neural networks, we can effectively predict an organism’s dynamic response to a stimulus based on an initial dataset with relatively few samples. We present both anin silicoproof of principle, based on a model that simulates viral propagation, and anin vitrocase study, tracking the dynamics ofAspergillus nidulans’BrlA transcript in response to antifungal agent micafungin. Oursilicoexperiment was conducted using a highly noisy dataset with only 25 replicates. This proof of principle shows that this method can operate on biological datasets, which often have high variance and few replicates. Ourin silicovalidation achieved a maximum R2value of approximately 0.95 on our highly noisy, stochastically simulated data. Ourin vitrovalidation achieves an R2of 0.71. As with any machine learning application, this method will work better with more data; however, both of our applications attain acceptable validation metrics with very few biological replicates. Thein vitroexperiments also revealed a novel paradoxical dose-response effect: transcriptional upregulation byAspergillus nidulansBrlA is highest at an intermediate dose of 10 ng/mL and is reduced at both higher and lower concentrations of micafungin.
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- Award ID(s):
- 2006189
- PAR ID:
- 10597856
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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