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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. 

ABSTRACT Septation in filamentous fungi is a normal part of development, which involves the formation of cross-hyphal bulkheads, typically containing pores, allowing cytoplasmic streaming between compartments. Based on previous findings regarding septa and cell wall stress, we hypothesized that septa are critical for survival during cell wall stress. To test this hypothesis, we used known Aspergillus nidulans septation-deficient mutants (Δ sepH , Δ bud3 , Δ bud4 , and Δ rho4 ) and six antifungal compounds. Three of these compounds (micafungin, Congo red, and calcofluor white) are known cell wall stressors which activate the cell wall integrity signaling pathway (CWIS), while the three others (cycloheximide, miconazole, and 2,3-butanedione monoxime) perturb specific cellular processes not explicitly related to the cell wall. Our results show that deficiencies in septation lead to fungi which are more susceptible to cell wall-perturbing compounds but are no more susceptible to other antifungal compounds than a control. This implies that septa play a critical role in surviving cell wall stress. IMPORTANCE The ability to compartmentalize potentially lethal damage via septation appears to provide filamentous fungi with a facile means to tolerate diverse forms of stress. However, it remains unknown whether this mechanism is deployed in response to all forms of stress or is limited to specific perturbations. Our results support the latter possibility by showing that presence of septa promotes survival in response to cell wall damage but plays no apparent role in coping with other unrelated forms of stress. Given that cell wall damage is a primary effect caused by exposure to the echinocandin class of antifungal agents, our results emphasize the important role that septa might play in enabling resistance to these drugs. Accordingly, the inhibition of septum formation could conceivably represent an attractive approach to potentiating the effects of echinocandins and mitigating resistance in human fungal pathogens.