Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents

Author(s)

Komoto, Tatiana Takahasi ; Bitencourt, Tamires Aparecida ; Silva, Gabriel ; Beleboni, Rene Oliveira ; Marins, Mozart ; Fachin, Ana Lucia

• Document type: Journal article
• Source: Evidence-based Complementary and Alternative Medicine; v. 2015, p. 7-pg., 2015-01-01.

Abstract

Trichophyton rubrumis themost common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid alpha-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8 mu g/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60 mu M to alpha-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets. (AU)

• FAPESP's process: 12/02920-7 - Transcriptome of the dermatophyte Trichophyton rubrum in response to antifungal transchalcona in culture conditions that simulate infection
• Grantee: Tamires Aparecida Bitencourt
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/03845-9 - Transcriptome of the dermatophyte Trichophyton rubrum in response to antifungal transchalcona in culture conditions that simulate human skin infection
• Grantee: Ana Lucia Fachin Saltoratto
• Support Opportunities: Regular Research Grants