New aspects on the role of extracellular vesicle components from human pathogenic fungi in the transmission of stimuli and in the course of the infection

• Grant number: 22/11123-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Rosana Puccia
• Grantee: Rosana Puccia
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alexandre Keiji Tashima ; Erix Alexander Milán Garcés ; Evandro Luiz Duarte ; Marcos Antonio de Oliveira ; Maria Aparecida Juliano ; Wagner Luiz Batista

Abstract

Extracellular vesicles (EVs) are membranous components involved in a non-classical secretion mechanism reported in all kingdoms. EVs carry to the extracellular environment hundreds of molecules in a concentrated and protected way, thus promoting a sophisticated kind of distant cell signaling. Our group pioneered the description of EV proteins, lipids, oligo and polysaccharides from Paracoccidiodes and of EV RNAs from several fungal species. We have recently shown that vEVs from P. brasiliensis vPb18 (virulent) can revert the stress sensitivity phenotype/genotype from its attenuated variant. EVs from the Pb18 variants distinctly stimulated macrophages and prompted infection exacerbation in the murine model. We have also shown that stress conditions modulated the EV proteome and transcriptome from Paracoccidioides and Candida albicans. The present project aims to obtain original and complementary data on the role of EVs from P. brasiliensis virulent/attenuated Pb18 in the stimulus of murine macrophages and dendritic cells, human neutrophils, and in the immuneprophylaxis of murine paracoccidioidomycosis. We search for original results on the intraspecies signaling features of EVs obtained from Paracoccidioides and Candida albicans cultivated under stress. In addition, we will evaluate the fungicidal effect of inhibitors of the antioxidant Cys-1 peroxiredoxin enzyme PbPrx1, which is a Paracoccidioides EV component our group previously characterized. This enzyme has substrate preference for organic hydroperoxides and can potentially protect the fungus against reactive oxygen and nitrogen species. This project involves five graduate students and a posdoc. (AU)