Identification and characterization of carbohydrates present in extracellular vesicles of Candida auris in response to antifungal exposure

• Grant number: 22/09523-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Gabriel Ernesto Silva Trentin
• 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

Candida auris is a newly discovered pathogen that has attracted international media attention due to its multidrug resistance to classic antifungals used in the treatment of candidiasis and prevalence in intensive care units. The successful establishment of the infection is due to strategies developed by this fungus to deal with defensive molecules secreted by the host. During the course of the infectious process, the release of extracellular vesicles (EVs) is considered an alternative to the canonical mechanisms of biomolecule secretion that favors the interaction of the fungus with the host microenvironment and it is associated with immunomodulatory properties. Fungal EVs are composed of a lipid bilayer and transport lipids, proteins, nucleic acids, pigments and carbohydrates, being crucial for the pathophysiological process. Preliminary results from our research group verified changes in the concentrations and populations of EVs of C. auris, when it was subjected to stress caused by antifungal agents. The observed changes motivate the proposal of this project to evaluate the production of EVs in the face of exposure to different antifungals, as well as the characterization of the carbohydrates present. Specifically, we propose to fulfill the following objectives: (1) To characterize the EVs produced by C. auris against antifungals; (2) Isolate and characterize the internal carbohydrates of the EVs produced; (3) Identify carbohydrates present on the surface of the EVs obtained. Our expectation is that there are carbohydrates present internally and externally in the VEs of C. auris and that the identification of such biomolecules can provide crucial information that helps to justify the multidrug resistance of this pathogen.