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The Transcriptional Profile of Trichophyton rubrum Co-Cultured with Human Keratinocytes Shows New Insights about Gene Modulation by Terbinafine

1
Biotechnology Unit, University of Ribeirão Preto-UNAERP, Av. Costábile Romano 2201, Ribeirão Preto 14960-900, SP, Brazil
2
National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-Based Therapy, Ribeirão Preto 14051-140, SP, Brazil
3
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
4
Center for Integrative System Biology-CISBi-NAP/USP, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
5
Center for Medical Genomics, University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14015-010, SP, Brazil
*
Author to whom correspondence should be addressed.
Pathogens 2019, 8(4), 274; https://doi.org/10.3390/pathogens8040274
Received: 6 November 2019 / Revised: 20 November 2019 / Accepted: 22 November 2019 / Published: 29 November 2019
The dermatophyte Trichophyton rubrum is the main causative agent of dermatophytoses worldwide. Although a superficial mycosis, its incidence has been increasing especially among diabetic and immunocompromised patients. Terbinafine is commonly used for the treatment of infections caused by dermatophytes. However, cases of resistance of T. rubrum to this allylamine were reported even with the efficacy of this drug. The present study is the first to evaluate the effect of terbinafine using a co-culture model of T. rubrum and human keratinocytes, mimicking a fungus-host interaction, in conjunction with RNA-seq technique. Our data showed the repression of several genes involved in the ergosterol biosynthesis cascade and the induction of genes encoding major facilitator superfamily (MFS)- and ATP-binding cassette superfamily (ABC)-type membrane transporter which may be involved in T. rubrum mechanisms of resistance to this drug. We observed that some genes reported in the scientific literature as candidates of new antifungal targets were also modulated. In addition, we found the modulation of several genes that are hypothetical in T. rubrum but that possess known orthologs in other dermatophytes. Taken together, the results indicate that terbinafine can act on various targets related to the physiology of T. rubrum other than its main target of ergosterol biosynthetic pathway. View Full-Text
Keywords: antifungal; allylamine; dermatophyte; ergosterol; ERG1; NGS; resistance antifungal; allylamine; dermatophyte; ergosterol; ERG1; NGS; resistance
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Petrucelli, M.F.; Matsuda, J.B.; Peroni, K.; Sanches, P.R.; Silva, W.A., Jr.; Beleboni, R.O.; Martinez-Rossi, N.M.; Marins, M.; Fachin, A.L. The Transcriptional Profile of Trichophyton rubrum Co-Cultured with Human Keratinocytes Shows New Insights about Gene Modulation by Terbinafine. Pathogens 2019, 8, 274.

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