Role of extracellular vesicles from Cryptococcus neoformans in the cellular communication

• Grant number: 23/14259-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2023
• End date: October 31, 2024
• 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

Mechanisms involved in cell-cell communication are important for pathogenic fungi during their adaptation to hostile environments and harsh conditions (differences in pH, incubation temperature, radiation, and inhibitory molecules), allowing their survival in the host and consequently their success in infection. This interaction, even at a distance, can regulate various processes, some of which are directly connected with virulence factors. Extracellular vesicles (EVs) have been studied for their role in fungal communication in several pathogenic fungi, such as Candida, Aspergillus, Paracoccidioides, and Cryptococcus. EVs are lipid bilayer structures that carry a concentrated cargo of proteins, enzymes, nucleic acids, and other molecules, which in Cryptococcus spp. EVs can transport important virulence factors, such as urease, laccase, melanin, and glucuronoxylomannan (GXM). Cryptococcus neoformans is the fungus responsible for cryptococcosis, a disease that can be fatal, mainly in immunosuppressed individuals. Melanin is a pigment easily detectable with important characteristics that confer fungal protection against radiation, resistance to antifungals, exhibit antioxidant activity, and contribute to cell wall structure. Melanization of Cryptococcus spp. can be induced in vitro, depending on the presence of a precursor like L-DOPA (3,4-dihydroxyphenylalanine) and laccase activity. Since melanin is transported by EVs, we propose to extract EVs from melanized C. neoformans and add them to non-melanized cultures of C. neoformans and C. gattii, exploring a possible melanization induction and differences in gene expression patterns, cell morphology, viability, and characterization of EVs produced in the fungal cultures. In this way, we hope to shed light on fungal communication by EVs and determine whether the induced responses are species-specific or similar in fungi of the genus Cryptococcus.