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Background   Trichophyton rubrum  is the main etiological agent of skin and nail infections worldwide. Because of its keratinolytic activity and anthropophilic nature, infection models based on the addition of protein substrates have been employed to assess transcriptional profiles and to elucidate aspects related to host-pathogen interactions. Chalcones are widespread compounds with pronounced activity against dermatophytes. The toxicity of  trans -chalcone towards  T. rubrum  is not fully understood but seems to rely on diverse cellular targets. Within this context, a better understanding of the mode of action of  trans -chalcone may help identify new strategies of antifungal therapy and reveal new chemotherapeutic targets. This work aimed to assess the transcriptional profile of  T. rubrum  grown on different protein sources (keratin or elastin) to mimic natural infection sites and exposed to  trans -chalcone in order to elucidate the mechanisms underlying the antifungal activity of  trans- chalcone.    Results  Overall, the use of different protein sources caused only slight differences in the transcriptional profile of  T. rubrum . The main differences were the modulation of proteases and lipases in gene categories when  T. rubrum  was grown on keratin and elastin, respectively. In addition, some genes encoding heat shock proteins were up-regulated during the growth of  T. rubrum  on keratin. The transcriptional profile of  T. rubrum  exposed to  trans -chalcone included four main categories: fatty acid and lipid metabolism, overall stress response, cell wall integrity pathway, and alternative energy metabolism. Consistently,  T. rubrum  Mapk was strongly activated during the first hours of  trans -chalcone exposure. Noteworthy,  trans- chalcone inhibited genes involved in keratin degradation. The results also showed effects of  trans -chalcone on fatty acid synthesis and metabolic pathways involved in acetyl-CoA supply.    Conclusion  Our results suggest that the mode of action of  trans -chalcone is related to pronounced changes in fungal metabolism, including an imbalance between fatty acid synthesis and degradation that interferes with cell membrane and cell wall integrity. In addition, this compound exerts activity against important virulence factors. Taken together,  trans -chalcone acts on targets related to dermatophyte physiology and the infection process.    Electronic supplementary material  The online version of this article (10.1186/s12864-019-5792-0) contains supplementary material, which is available to authorized users.

bmc genomics

Trans-chalcone activity against Trichophyton rubrum relies on an interplay between signaling pathways related to cell wall integrity and fatty acid metabolism