Role of extracellular vesicles from Cryptococcus neoformans in the cellular communication

• Grant number: 24/15805-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2024
• Effective date (End): October 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Henrique Trevisam de Oliveira
• 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

Cell-to-cell communication is essential for the pathogenic fungi adaptation to hostile environments and stress conditions, such as changes in pH, temperature, radiation and the presence of inhibitors, which facilitates their survival and successful infection. Cryptococcus neoformans, which causes cryptococcosis, a serious and potentially fatal disease, especially in immunecompromised individuals, uses extracellular vesicles (EVs) for intercellular communication. These EVs are found in several pathogenic fungi, such as Candida, Aspergillus, Paracoccidioides and Cryptococcus, carrying a variety of molecules, including proteins, enzymes, nucleic acids and other molecules. In Cryptococcus, these EVs may contain important virulence factors, such as urease, laccase, melanin and glucuronoxylomannan (GXM). Melanin, a detectable pigment, protects the fungus against radiation, increases resistance to antifungals and has antioxidant properties and participate in the structure of the cell wall. Melanization of Cryptococcus spp. strains can be induced in vitro in the presence of L-DOPA (3,4 dihydroxyphenylalanine) and laccase activity. In this study, we intend to extract EVs from melanized C. neoformans and add them to cultures of non-melanized C. neoformans and C. gattii to investigate the induction of melanization and analyze differences in gene expression, cell morphology, viability and characteristics of the EVs. In addition, we propose to evaluate the role of EVs in the transfer of other virulence factors, such as the polysaccharide capsule composed of GXM. The aim is to elucidate the mechanisms of fungal communication mediated by EVs and determine whether the responses are species-specific or common among fungi of the genus Cryptococcus. (AU)