Unveiling the Role of StuA in Transcription Regulation in Trichophyton rubrum: From Global Regulation Dynamics to the pH-Responsive Program Control.

The dermatophyte Trichophyton rubrum is the primary causative agent of a cutaneous disease known as dermatophytosis. To establish an infection, this fungus coordinates many mechanisms related to biochemical processes, physiological adaptation, and transcriptional networks. Transcription factors (TFs) are the main proteins that elicit biological responses when T. rubrum interacts with keratinized tissues and promotes defense responses to prevent fungal colonization. In this study, we investigated the role of the TF StuA, a recently described T. rubrum protein, in controlling this fungal transcriptional program in response to glucose and keratin. This approach, based on RNA sequencing data, revealed at least 33 TF genes differentially expressed in glucose or keratin. We also showed that StuA regulates the pH signaling transcription factor, PacC, a relevant TF recruited for keratin assimilation in T. rubrum. Furthermore, we demonstrated that StuA modulates positively pacC and influences alternative splicing events of pacC transcripts in keratin cultures. Our findings revealed that StuA represses pacC transcription in a co-culture with keratinocytes and modulates the expression of the pal pathway genes, besides suggesting that StuA is pivotal for pH recognition responses and nutrient assimilation in the host. As a follow-up study, our results shed light on discovering new targets to treat dermatophytosis and elucidating transcriptional networks that are fundamental to T. rubrum pathogenesis.