Transcription Factor Heterodimer Interacted with a Cyclin Orchestrates Fungal Cell Wall Homeostasis, Development, and Virulence in an Insect Fungal Pathogen

The cell wall integrity is crucial for fungal development, adaptation to adverse environments, and virulence. Here, a transcription factor (TF) heterodimer, BbOsrR2-BbOsrR3, in complex with a cyclin BbClp1 was found to orchestrate cell wall homeostasis in an entomopathogenic fungus Beauveria bassiana. The ΔBbOsrR2 mutant displayed increased sensitivity to cell wall stress, with reduced β-1,3-glucan and chitin contents. These opposite phenotypes were examined in the ΔBbOsrR3 and ΔBbClp1 mutants. The two TFs, BbOsR2 and BbOsrR3, targeted distinct genes in response to cell wall stress. Phosphorylation of the two TFs was interdependent and regulated by BbClp1, which was linked to their transcription activities. Two BbOsrR2 targets, BbGlu and BbMgn, were found to negatively and positively mediate cell wall integrity, and conidial germination and virulence, respectively, which greatly contributed to the BbOsrR2 and BbOsrR3-controlled cell wall homeostasis, and fungal development and virulence. These results demonstrate a regulatory network orchestrating fungal cell wall homeostasis and virulence.