Transcription factors and cellular signaling pathways in pathogenicity and modulation of the immune response

• Grant number: 24/17493-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Antonio Rossi Filho
• Grantee: Mayara Itala Geronimo de Azevedo
• Host 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

Among the essential gene groups for developing the infectious process, transcription factors responsible for regulating gene activity stand out. Our group demonstrated the relationship between the transcription factor PacC and the growth of the dermatophyte T. interdigitale in human nails in vitro, confirming its role in fungal pathogenicity. Studying the regulatory mechanisms exerted by transcription factors and their effect on the other genes in T. rubrum will favor understanding the pathogen-host interaction processes. In addition to exploring the individual function of genes, the evaluation of cell signaling pathways activated in response to stressful situations can also generate clues for understanding the pathogen's adaptation to the site of infection. Studying these pathways contributes to understanding different processes, including the modulation mechanisms of the host's immune response, which aim to superimpose the infection process. Recent data published by us present the modulation of genes that code for LysM domains in T. rubrum in response to keratin, a substrate present in the host. Proteins containing these domains probably act by masking pathogens' cell wall components to confuse the host's immune response, having a relevant role in the pathogenicity of dermatophytes. The initial process of infection by dermatophytes may guide the systematic understanding of the pathways activated due to the association of the pathogen with the host substrate and the identification of factors related to the immune response. For this, we propose using infection systems in human cells, using techniques already used in T. rubrum, and also aiming to reveal new therapeutic targets.