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Gene expression profile involved in signal transduction pathways for injuries caused in cell wall after exposition Trichophyton rubrum to antifungals

Grant number: 16/11888-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2016
Effective date (End): October 31, 2017
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal researcher:Ana Lucia Fachin Saltoratto
Grantee:Igor Sawasaki Moreli
Home Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil

Abstract

Trichophyton rubrum is a dermatophyte fungus prevalent in superficial infections in Brazil and worldwide, can also cause deep infections in immunocompromised patients. Despite the clinical importance of this dermatophyte, knowledge about the molecular factors involved in the infection process and the response to treatment with antifungal agents is still limited. Currently, commercial antifungal present as primary targets in the fungal cell: ergosterol biosynthesis, nucleic acids and the cell wall. The cell wall is essential for cell viability and is a constituent present only in the fungal cell, a fact which makes it a very attractive target antifungal. Despite the importance of the cell wall there is only antifungal licensed for clinical use that operates this target, which is caspofungin. Gene expression experiments in large scale of Aspergillus niger in the presence of caspofungin (which inhibit synthesis of the beta-1,3 glucan) and also in the presence of fenpropimofe (which inhibit synthesis of ergosterol) showed that these compounds induce directly or indirectly the genes of the cell wall integrity pathway (CWI). Likewise, the gene expression analysis of T. rubrum exposed to antifungal trans-chalcone (which operates in ergosterol synthesis and cell wall), previously held by our research group showed that this compound also modulated genes encoding signal transducers involved in cell wall integrity (CWI). This data, combined with knowledge have been described in fungi model allowed the deduction of a hypothetical model for the adaptation of T. rubrum in response to stress caused by trans-chalcone, which involves cell wall integrity pathway (CWI). Thus, the aim of this project is to analyze the expression of genes linked to signaling pathways involved in cell wall integrity after exposure T. rubrum to sublethal concentrations of drugs that act on the cell wall and ergosterol and compares them with the effect caused by the trans-chalcone.

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