The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum
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Published:2023-02-20
Issue:2
Volume:9
Page:275
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ISSN:2309-608X
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Container-title:Journal of Fungi
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language:en
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Short-container-title:JoF
Author:
Galvão-Rocha Flaviane M.1, Rocha Carlos H. L.1, Martins Maíra P.1ORCID, Sanches Pablo R.1ORCID, Bitencourt Tamires A.1, Sachs Matthew S.2ORCID, Martinez-Rossi Nilce M.1ORCID, Rossi Antonio1ORCID
Affiliation:
1. Department of Genetics, Ribeirao Preto Medical School, University of São Paulo, USP, Ribeirao Preto 14049-900, SP, Brazil 2. Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA
Abstract
The dermatophyte Trichophyton rubrum is responsible for most human cutaneous infections. Its treatment is complex, mainly because there are only a few structural classes of fungal inhibitors. Therefore, new strategies addressing these problems are essential. The development of new drugs is time-consuming and expensive. The repositioning of drugs already used in medical practice has emerged as an alternative to discovering new drugs. The antidepressant sertraline (SRT) kills several important fungal pathogens. Accordingly, we investigated the inhibitory mechanism of SRT in T. rubrum to broaden the knowledge of its impact on eukaryotic microorganisms and to assess its potential for future use in dermatophytosis treatments. We performed next-generation sequencing (RNA-seq) to identify the genes responding to SRT at the transcript level. We identified that a major effect of SRT was to alter expression for genes involved in maintaining fungal cell wall and plasma membrane stability, including ergosterol biosynthetic genes. SRT also altered the expression of genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress. Our findings provide insights into a specific molecular network interaction that maintains metabolic stability and is perturbed by SRT, showing potential targets for its strategic use in dermatophytosis.
Funder
São Paulo Research Foundation National Council for Scientific and Technological Development Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Subject
Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)
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