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The functionality of the PacC transcription factor in the pH response pathway in dermatophytes

Grant number: 21/04263-2
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2021
Effective date (End): April 30, 2025
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal researcher:Nilce Maria Martinez-Rossi
Grantee:João Neves da Rocha Fonseca
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/22596-9 - Molecular mechanisms associated with pathogenicity and resistance in fungi: strategies for treating dermatophytosis, AP.TEM

Abstract

Signal transduction pathways are of primary importance in the context of the parasitic interaction that some dermatophyte fungi develop with humans. Such infections are difficult to treat and represent a clinical issue of great relevance nowadays, especially in vulnerable or aging populations. By responding to specific stimuli from the environment, transduction pathways can modulate cellular mechanisms of resistance, virulence, and adaptive response. Ultimately, they produce phenotypic changes through the control of gene expression. The pH sensing in fungi is a conserved mechanism exercised by the signaling cascade of the pal genes, which are associated with the transcription factor PacC to promote the differential expression of target genes. Thus, fungal metabolism can be altered to function more efficiently in acidic or alkaline conditions. A relationship between the response pathways to pH and the acquisition of inorganic phosphate (Pi), known for some filamentous fungi, is assumed as a hypothesis in this work for dermatophytes. The importance of the PacC protein has been progressively demonstrated in these fungi through a mutant produced in our laboratory for the H6 strain of Trichophyton interdigitale. Preliminary data indicate that this factor is necessary for the growth of the species in nails and for the capacity of keratin degradation, which is also involved in the glycosylation of proteins. Considering these aspects, the main objective of this project is to invest in the global analysis of the transcriptome (RNA-Seq) of the H6 and ”pacC strains of T. interdigitale in order to establish a pH-Pi relationship in dermatophytes, also considering possible crosstalks with other relevant biological processes. In addition, comparative analyzes with the data already available for the species T. rubrum will be explored. This is intended to reveal regulatory circuits involved in the processes of environmental sensing and the pathogenicity of dermatophytes. (AU)

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