Antidepressant Sertraline Modulates the Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis

Background/Objectives: Dermatophytosis, a prevalent fungal infection of keratinized tissues, is primarily caused by the filamentous fungus Trichophyton rubrum. Sertraline (SRT), an antidepressant with antifungal activity, has already demonstrated therapeutic potential against this fungus. Elucidating the effects of SRT may provide insights into its mechanism of action and fungal adaptation to this drug. Differential gene expression and alternative splicing (AS) facilitate fungal adaptations to various environmental conditions. This study aimed to provide a comprehensive overview of AS events and their implications in T. rubrum cultivated under sub-inhibitory concentrations of SRT. Method: The transcriptome of T. rubrum challenged with SRT was analyzed to detect AS events. Results: RNA-seq analysis revealed that SRT affected transcriptional and post-transcriptional events in numerous T. rubrum genes, including those encoding transcription factors, kinases, and efflux pumps. Among the AS events, intron retention was predominant. After 12 h of SRT exposure, intron-3 retention levels in the serine/arginine protein kinase mRNA transcripts were significantly increased compared with those in the control. This new isoform would produce a putative protein that partially lost its phosphotransferase domain. Conclusions: These findings highlight the potential mechanisms of action of SRT, and suggest how T. rubrum adapts itself to this drug.