Deciphering the Functional Role of Protein Corona in Cellular Communication mediated by Fungal Extracellular Vesicles

• Grant number: 24/00403-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2024
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Lucas Fabrício Bahia Nogueira
• 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
• Associated scholarship(s): 25/07930-0 - Cyclic Antifungal Treatments as Modulators of Extracellular Vesicle Biogenesis and Protein Corona Formation in Biological Fluids, BE.EP.PD

Abstract

The study of fungal extracellular vesicles (EVs) is crucial to understanding the complex pathogen-host interactions, particularly in the face of the growing challenge of antifungal resistance. EVs play multifaceted roles, transporting biologically active molecules and influencing key biological mechanisms. A growing number of studies have investigated the occurrence of a phenomenon known as the protein corona, resulting from the spontaneous and nonspecific adsorption of proteins on the surface of EVs, thus influencing their functions. Consequently, this study suggests that proteins derived from the extracellular space can adsorb, forming a corona of peripheral proteins on the surface of fungal EVs. This prompts research into the role of this corona in fungal infections, questioning whether it has a specific biological function or it consists solely of contaminant proteins. Understanding the potential influence of these peripheral proteins on EVs is essential for a better grasp of pathogen-host interactions and the role of EVs in modulating the immune response. In this context, the investigated hypothesis highlights the influence of the protein corona on the interactions of fungal EVs with the host immune system, suggesting responses and modifications in the biological properties of these structures. The main objective is to elucidate how the protein corona in EVs from Paracoccidioides brasiliensis and Aspergillus fumigatus influences macrophage activity, playing a critical role in the host's immune response during fungal infections. To achieve these objectives, we propose: (i) isolating, characterizing, and investigating the formation of the protein corona on these EVs by evaluating the proteomic profile of the EV surface; (ii) isolating and identifying proteins composing this corona using antibody-modified magnetic particles (dynabeads); (iii) examining the role of the protein corona in macrophage immunomodulation through cultivation, using both EVs with the corona removed and the supernatant containing these isolated proteins; (iv) compare EVs from both fungal species, identifying significant differences in protein composition and their impact on macrophage activity. The development of this postdoctoral proposal will provide insight into pathogen-host relationship mechanisms, contributing to the development of potential therapeutic strategies for treating fungal infections.