Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction

Abstract

The dermatophyte <i>Trichophyton rubrum</i> is the major fungal pathogen of skin, hair, and nails that uses keratinized substrates as the primary nutrients during infection. Few strategies are available that permit a better understanding of the molecular mechanisms involved in the interaction of <i>T. rubrum</i> with the host because of the limitations of models mimicking this interaction. Dual RNA-seq is a powerful tool to unravel this complex interaction since it enables simultaneous evaluation of the transcriptome of two organisms. Using this technology in an in vitro model of co-culture, this study evaluated the transcriptional profile of genes involved in fungus-host interactions in 24 h. Our data demonstrated the induction of glyoxylate cycle genes, <i>ERG6</i> and <i>TERG_00916</i>, which encodes a carboxylic acid transporter that may improve the assimilation of nutrients and fungal survival in the host. Furthermore, genes encoding keratinolytic proteases were also induced. In human keratinocytes (HaCat) cells, the <i>SLC11A1</i>, <i>RNASE7</i>, and <i>CSF2</i> genes were induced and the products of these genes are known to have antimicrobial activity. In addition, the <i>FLG</i> and <i>KRT1</i> genes involved in the epithelial barrier integrity were inhibited. This analysis showed the modulation of important genes involved in <i>T. rubrum</i>⁻host interaction, which could represent potential antifungal targets for the treatment of dermatophytoses.