Analysis of gene expression changes in Trichophyton rubrum after skin interaction

Abstract

Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most common agent of superficial mycoses. In this study, T. rubrum infection was modelled by adding human skin sections to a limited medium containing glucose and cDNA microarrays were used to monitor T. rubrum gene expression patterns on a global level. We observed that exposure to human skin resulted in upregulation of the expression levels of T. rubrum genes related to many cellular and biological processes, including transcription and translation, metabolism and secondary transport, the stress response, and signalling pathways. These results provide a reference set of T. rubrum genes whose expression patterns change upon infection and reveal previously unknown genes that most likely correspond to proteins that should be considered as virulence factor candidates and potential new drug targets for T. rubrum infection.

Fig. 1.

KMC clustering of microarray data and identification of genes with similar transcriptional profiles. (a) A total of 768 genes were clustered on the basis of their expression profiles when cultured with human skin sections relative to their expression profiles when cultured in LM across five time points. Each gene belonged to one of the four KMC clusters. Each gene’s expression values were standardized to have a median of 0 and an sd of 1 across the time points from 0 to 12 h. The lighter colour in the cluster dendrogram is correlated with a higher expression level. (b) Mean expression profiles of the genes within each cluster. To obtain each profile, a sum of the expression values across the five time points for each gene was standardized to 1. Next, the time-course values for all genes in each cluster were summed and the summed value for the five time points for each cluster was scaled to 1. log2(H/C): for each gene in KMC clusters, log2(H/C) refers to log2 (expression level cultured in human skin sections/expression level cultured in LM).