Gene Expression Response ofTrichophyton rubrumduring Coculture on Keratinocytes Exposed to Antifungal Agents
Trichophyton rubrumis the most 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 ofT. rubrumcocultured with keratinocytes and treated with the flavonoidtrans-chalcone and the glycoalkaloidα-solanine. Both substances showed a marked antifungal activity againstT. rubrumstrain CBS (MIC = 1.15 and 17.8 µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50values of 44.18 totrans-chalcone and 61.60 µM toα-solanine. The interaction of keratinocytes withT. rubrumconidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporterTruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, andTruMDR2 genes. Furthermore, thetrans-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.