Transcription factor CreA is involved in the inverse regulation of biofilm formation and asexual development through distinct pathways in Aspergillus fumigatus

Abstract

The exopolysaccharide galactosaminogalactan (GAG) contributes to biofilm formation and virulence in the pathogenic fungus Aspergillus fumigatus. Increasing evidence indicates that GAG production is inversely linked with asexual development. However, the mechanisms underlying this regulatory relationship are unclear. In this study, we found that the dysfunction of CreA, a conserved transcription factor involved in carbon catabolite repression in many fungal species, causes abnormal asexual development (conidiation) under liquid‐submerged culture conditions specifically in the presence of glucose. The loss of creA decreased GAG production independent of carbon sources. Furthermore, CreA contributed to asexual development and GAG production via distinct pathways. CreA promoted A. fumigatus GAG production by positively regulating GAG biosynthetic genes (uge3 and agd3). CreA suppressed asexual development in glucose liquid‐submerged culture conditions via central conidiation genes (brlA, abaA, and wetA) and their upstream activators (flbC and flbD). Restoration of brlA expression to the wild‐type level by flbC or flbD deletion abolished the abnormal submerged conidiation in the creA null mutant but did not restore GAG production. The C‐terminal region of CreA was crucial for the suppression of asexual development, and the repressive domain contributed to GAG production. Overall, CreA is involved in GAG production and asexual development in an inverse manner.

The basic leucine zipper transcription factor MeaB is critical for biofilm formation, cell wall integrity, and virulence in Aspergillus fumigatus

“…1C ). Considering the regulatory mechanism of A. fumigatus, CreA in biofilm formation and cell wall integrity has been elucidated ( 44 , 45 ). Our results of HapB in cell wall integrity and biofilm formation (Fig.…”

“…Many proteins playing a certain role in cell wall biogenesis are also involved in the regulation of biofilm GAG biosynthesis. Apart from the aforementioned transcription factors SomA and MeaB, a salient case is that of CreA; the carbon catabolite repressor not only regulated cell wall homeostasis ( 44 ) but was also closely associated with galactosaminogalactan-mediated biofilm formation ( 45 ). Here, our data indicate that loss of the CCAAT-binding transcriptional regulator, HapB, causes severe defects in congo red resistance and GAG detection.…”