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Volume 16
Issue 2
10.3390/genes16020146
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Carlos H. Lopes Rocha
,
Flaviane M. Galvão Rocha
,
Pablo R. Sanches
,
Antonio Rossi
and
Nilce M. Martinez-Rossi
*
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
*
Author to whom correspondence should be addressed.
Genes 2025, 16(2), 146; https://doi.org/10.3390/genes16020146
Submission received: 14 December 2024 / Revised: 17 January 2025 / Accepted: 21 January 2025 / Published: 24 January 2025
(This article belongs to the Special Issue Advances in Genomics of Pathogenic Fungi)
Versions Notes

Abstract

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.
Keywords: dermatophytosis; sertraline; alternative splicing; intron retention; kinase; pathogenic fungi dermatophytosis; sertraline; alternative splicing; intron retention; kinase; pathogenic fungi

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MDPI and ACS Style

Rocha, C.H.L.; Galvão Rocha, F.M.; Sanches, P.R.; Rossi, A.; Martinez-Rossi, N.M. The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis. Genes 2025, 16, 146. https://doi.org/10.3390/genes16020146

AMA Style

Rocha CHL, Galvão Rocha FM, Sanches PR, Rossi A, Martinez-Rossi NM. The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis. Genes. 2025; 16(2):146. https://doi.org/10.3390/genes16020146

Chicago/Turabian Style

Rocha, Carlos H. Lopes, Flaviane M. Galvão Rocha, Pablo R. Sanches, Antonio Rossi, and Nilce M. Martinez-Rossi. 2025. "The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis" Genes 16, no. 2: 146. https://doi.org/10.3390/genes16020146

APA Style

Rocha, C. H. L., Galvão Rocha, F. M., Sanches, P. R., Rossi, A., & Martinez-Rossi, N. M. (2025). The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte Trichophyton rubrum: A Comprehensive Analysis. Genes, 16(2), 146. https://doi.org/10.3390/genes16020146

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