Abstract
The dermatophyte Trichophyton rubrum 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 T. rubrum 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, ERG6 and TERG_00916, 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 SLC11A1, RNASE7, and CSF2 genes were induced and the products of these genes are known to have antimicrobial activity. In addition, the FLG and KRT1 genes involved in the epithelial barrier integrity were inhibited. This analysis showed the modulation of important genes involved in T. rubrum–host interaction, which could represent potential antifungal targets for the treatment of dermatophytoses.
Highlights
Dermatophytoses are superficial infections of keratinized tissues caused by a group of filamentous fungi called dermatophytes [1]
With the advent of this technology and the published sequence of the T. rubrum genome, the present study evaluated the transcriptional profile of T. rubrum co-cultured with human keratinocytes (HaCat) for 24 h by dual RNA-seq to identify important genes involved in the host defense and fungal pathogenicity in order to increase our understanding of the molecular aspects of this interaction
We found that the modulation of the LAP2 and Dipeptidyl peptidase V (DPPV) genes involved in the production of keratinolytic proteases that are important for the virulence of this dermatophyte
Summary
Dermatophytoses are superficial infections of keratinized tissues caused by a group of filamentous fungi called dermatophytes [1]. Despite the importance of these infections in clinical practice, knowledge of the molecular mechanisms involved in the dermatophyte-host interaction is limited, possibly because of the technical difficulties of the models mimicking this interaction, as well as the lack of genetic tools that allow for a more in-depth study of these organisms [7] This scenario has been changing with the sequencing of mixed transcriptomes, called dual RNA-seq, an approach widely used for the study of the complex interaction that exists between the host and pathogen [8] including bacteria [9], viruses [10], and fungi [11,12]. The inhibition of FLG and KRT1 genes whose products are directly involved in the maintenance of skin barrier integrity was observed
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