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

Autor(es)

Petrucelli, Monise Fazolin ^[1] ; Matsuda, Josie Budag ^[1] ; Peroni, Kamila ^[2] ; Sanches, Pablo Rodrigo ^[3] ; Silva, Jr., Wilson Araujo ^{[3, 2, 4, 5]} ; Beleboni, Rene Oliveira ^[1] ; Martinez-Rossi, Nilce Maria ^[3] ; Marins, Mozart ^[1] ; Fachin, Ana Lucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Ribeirao Preto UNAERP, Biotechnol Unit, Av Costabile Romano 2201, BR-14960900 Ribeirao Preto, SP - Brazil

^[2] Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, NAP, Ctr Integrat Syst Biol CISBi, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Univ Hosp, Ctr Med Genom, BR-14015010 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PATHOGENS; v. 8, n. 4 DEC 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 16/22701-9 - "Estudo da resposta a antifúngicos e da interação fungo-hospedeiro do dermatofito Trichophyton rubrum utilizando diferentes modelos de infecção"
• Beneficiário: Ana Lucia Fachin Saltoratto
• Modalidade de apoio: Auxílio à Pesquisa - Regular