Iron homeostasis and expression of virulence factors in the genus Paracoccidioides: biotechnological applications

• Grant number: 19/23801-5
• Support type: Regular Research Grants
• Duration: September 01, 2020 - August 31, 2022
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Cooperation agreement: CONFAP - National Council of State Research Support Foundations
• Principal researcher: Fausto Bruno dos Reis Almeida
• Grantee: Fausto Bruno dos Reis Almeida
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Iron has a central position at the pathogen-host interface. Mammals have high affinity systems for iron sequestration from pathogens, and pathogen resistance to iron deprivation is a virulence factor. During iron deprivation, members of the Paracoccidioides complex, etiological agents of paracoccidioidomycosis disease induce iron acquisition systems, including siderophores production, heme and extracellular iron uptake, processes regulated by HapX transcription factor. Despite studies, little is known about the uptake mechanisms and synthesis of siderophores, molecules for extracellular iron uptake, heme uptake pathway of the hemoglobin molecule and genes that control iron homeostasis in this pathogen. In this context, we propose to do the following aims: to characterize at molecular level, Paracoccidioides mutants for the HapX gene; to characterize molecules involved in extracellular iron uptake and production of mutants silenced for them; to define the secretion pathway of extracellular iron-binding proteins; to investigate the role of extracellular vesicles during iron deprivation; to evaluate, in vitro, the production of inflammatory mediators and cellular activity of HapX gene-stimulated macrophages stimulated with Paracoccidioides; to explore new targets for antifungal therapy. (AU)