Role of fungal extracellular vesicles during cellular communication

• Grant number: 23/05800-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Renan Eugênio Araujo Piraine
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 21/06794-5 - Fungal extracellular vesicles: immunomodulation and cellular communication, AP.JP2

Abstract

Pathogenic fungi cause thousands of deaths each year. Extracellular vesicles (EVs) are structures formed by a lipid bilayer that carry in their interior proteins, nucleic acids, carbohydrates, pigments, and lipids. EVs are related to biofilm formation, stimuli of cytokine production, virulence transference, antifungal resistance, and cell-cell communication, contributing to pathogenicity and disease outcomes. Thus, understanding the functioning of these EVs can be fundamental for the development of new therapeutic and preventive strategies against fungal diseases. In this project, we will seek to determine the role of EVs from Paracoccidioides brasiliensis, Candida albicans, and Aspergillus fumigatus in cell communication and, subsequently, in the stimulation of cells of the immune system. For this, we will evaluate intra- and inter-species communication using methods of purification, isolation, quantification, and characterization of the EVs, evaluating (a) methods that induce fungal stress and their impact on the production of EVs; (b) absorption of EVs by fungal cells, changes in gene expression, and morphological aspects; and (c) single-cell analysis for a better understanding of the mechanisms involved in EV-mediated communication. Additionally, the role of EVs in stimulating macrophages will be evaluated, seeking to determine the production of inflammatory mediators and the role of receptors involved. Thus, we hope to determine which molecules are involved in communication via EVs by identifying the increase or decrease in the transcription of specific genes, the impact of the absorption of these vesicles by fungi, and the response mediated by EVs in cells of the immune system. The data obtained during the execution of this project will be important to the advancement of knowledge in the biology of fungi, which may be directly related to the discovery of new targets and therapies against pathogenic fungi.