Kinases and phosphotases involved in brain infection in Cryptococcus neoformans transported by extracellular vesicles: a necessary step to understand the host-pathogen interaction

• Grant number: 23/08258-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Agreement: National Research Foundation of Korea (NRF)
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Fausto Bruno dos Reis Almeida
• Principal researcher abroad: Yong-Sun Bahn
• Institution abroad: Yonsei University, South Korea
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Cryptococcus neoformans is an encapsulated fungal pathogen that causes fatal meningoencephalitis. Extracellular vesicles (EVs) play an important role in the biology of all domains of life, including fungi. In C. neoformans, they are required for the trafficking of molecules across the capsule and cell wall. The mechanisms by which C. neoformans modulate the immune response are still obscure, but our groups have studied kinases and phosphatases as regulators of brain infectivity in C. neoformans, and EVs as potential immunomodulators of fungal infections. Understanding the functions/effects of kinases and phosphatases related to the C. neoformans pathophysiology is critical for our comprehension of the host immune response against C. neoformans. In this proposal, we aim to determine the role of Kinases and phosphatases in EVs from C. neoformans on host immune response. More specifically, we propose to do the following aims: (1) To characterize the production of EVs from C. neoformans kinase and phosphatase mutants; (2) To assess the ability of EV production by C. neoformans kinase and phosphatase mutants to modulate host immune response; (3) To analyze the regulated expression of host mediators in macrophages infected by C. neoformans kinase and phosphatase mutants (4) To evaluate the fungicidal activity of macrophages exposed to C. neoformans kinase and phosphatase mutants. The development of this research proposal should directly contribute to our knowledge about the C. neoformans pathophysiology. Our expectation is to identify and propose new therapeutic targets to combat fungal infections. (AU)