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

Abstract

BackgroundCutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of T. rubrum exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST) collection by constructing one cDNA library and nine suppression subtractive hybridization libraries.ResultsThe 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.ConclusionIn 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.

In vitro susceptibility to antimycotic drug undecanoic acid, a medium-chain fatty acid, is nutrient-dependent in the dermatophyte Trichophyton rubrum

“…Furthermore, growth on keratin caused the overexpression of several proteases and membrane transporter protein genes that were only slightly expressed when the initial culture pH was adjusted to 8.0 and glucose was used as the carbon source . This suggests that the combination of a shift in the ambient pH and keratin as the carbon source is necessary to induce the expression of these genes (Peres et al 2010;Silveira et al 2010). Nevertheless, it is clear that an extracellular pH shift is not required for the inhibitory action of UDA on the H6 strain grown on Tween 20 or keratin cultures.…”

Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes

“…Despite their importance to public health, only a small number of antifungal drugs are available to treat dermatophytoses. Regardless of the availability and effectiveness of these drugs, a crucial problem concerning the treatment of fungal infections is the occurrence of resistance, where pathogens overcome host defence mechanisms (Martinez-Rossi et al, 2008;Peres et al, 2010Peres et al, , 2015Teles & Seixas, 2015).…”

Dermatófitos: interação patógeno-hospedeiro e resistência a antifúngicos

“…1 An alternative has been the use of culture media containing molecules of the host's microenvironment, such as keratin and other proteins, delineating the profile of gene and protein expression of T. rubrum in the use of these molecules as a source of nutrients. 35 These research studies have contributed to a greater understanding of the molecular strategies of dermatophytes as they use the host's molecules to survive. These studies also reveal interesting genes that should be evaluated as new targets for the development of antifungal drugs.…”