Alternative splicing in HSPs coding genes related to pathogenicity of dermatophyte Trichophyton rubrum

• Grant number: 22/15282-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Nilce Maria Martinez-Rossi
• Grantee: Maria Júlia Santos Saboya Pereira
• 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

Trichophyton rubrum is currently the main causative of dermatophytosis globally. The knowledge of molecular pathways that coordinate their biology is fundamental for developing new models of study about pathogenic fungi. Some crucial characteristics, such as the differential expression of stress response genes, provide adaptive value for the fungus allowing its maintenance in the face of conditions imposed by the parasite-host dynamics. Then, the choice of central molecules for resistance, virulence, and metabolic reprogramming as a target of studies is reinforced. Fungi notably employ Heat Shock Proteins (HSPs) to deal with stressful stimuli, as they play diverse roles in cellular homeostasis. Its main functions relate to processes such as signal transduction, breakdown of protein complexes, and correct protein folding. Factors that affect this homeostasis can be biotic or abiotic, causing conformational changes in proteins and recruiting the chaperone function of HSPs as an adaptive mechanism. The HSPs genes are differentially expressed according to the detection of conditions in the intra and extracellular media. Modulation of the expression of these genes and their respective paralogs can be complemented by alternative splicing at the post-transcriptional level to enrich the compensatory mechanisms that maintain the regulation of this pathway. The structure of genes and protein domains of HSPs are widely described in the literature and can be used as a starting point for developing a methodology that allows their correct identification and investigation in dermatophyte fungi. Thus, this work aims to validate the role of paralogous genes and splicing events in HSPs in the biological context of dermatophyte fungi. We will investigate the compensatory mechanisms involved in controlling the gene expression of HSPs in T. rubrum in response to abiotic cellular stress and infection models.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NEVES-DA-ROCHA, JOAO; SANTOS-SABOYA, MARIA J.; LOPES, MARCOS E. R.; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.. Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections. MICROORGANISMS, v. 11, n. 8, p. 25-pg., 2023-08-01. (21/04263-2, 19/22596-9, 22/15282-0)