Alternative splicing in genes coding for HSPs as a response to antifungals in the dermatophyte Trichophyton rubrum

Abstract

Trichophyton rubrum is one of the most prevalent species causing dermatophytosis worldwide. Its anthropophilic character, along with its sequenced genome, makes it a very useful model for studying the biology of pathogenic fungi - and, in association, also for the recognition of potential metabolic pathways as drug targets. In the context applied to antifungal therapies, biomolecules that perform central or multiple cellular functions are especially interesting, since a dysfunction associated with them would simultaneously hamper fungal survival and the eventual acquisition of resistance to treatment. A particular group of chaperone proteins, the HSPs (Heat Shock Proteins), correspond to such prerequisites: they constitute important ways of responding to cellular stress, acting in the regulation of the activity of other proteins in processes of folding and unfolding, maintenance of the native conformation and fragmentation of aggregates. In addition to this, the response to environmental stimuli in eukaryotic organisms reveals that the mechanism of gene regulation by alternative splicing may play a fundamental role in the formation of a wide phenotypic diversity in the proteome of cells, which hence confers adaptive advantages under adverse conditions. Therefore, the main objective of the present work is to verify the presence of isoforms related to stress response proteins (HSPs) in the dermatophyte species Trichophyton rubrum when exposed to antifungal drugs.