Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS) categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had not been previously deposited in public databases.In this study, we identified novel T. rubrum genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of T. rubrum to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs.Trichophyton rubrum is a cosmopolitan dermatophyte that colonizes human skin and nails and is the most prevalent cause of human dermatophytoses [1,2]. During the initial stages of the infection, dermatophytes induce the expression of adhesins and unspecific proteases and keratinases that have optimum activity at acidic pH values [3], which is probably because the human skin has an acidic pH value [4]. The secretion of these proteases, which have been identified as an important step in fungal pathogenicity and virulence [5,6], act on keratinous and nonkeratinous substrates to release peptides that are further hydrolyzed to amino acids by putative peptidases. The metabolism of some amino acids shifts the extracellular pH from acidic to alkaline values at which most known keratinolytic proteases have optimal enzymatic activity [7-9]. T. rubrum also responds to the environmental pH by altering its gene expression profile [9,10].Molecular studies have been performed with human pathogens such as Candida