In vitro and in vivo evaluation of synthetic organoselenium in the treatment of infections by Candida spp. and Cryptococcus spp.

• Grant number: 24/22772-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: March 31, 2029
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Kelly Ishida
• Grantee: Gislaine da Silva Rodrigues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Fungal diseases pose an increasing challenge due to the rise in immunocompromised populations and antifungal resistance. Candida spp. and Cryptococcus spp. are particularly concerning. Candida spp., commonly found in the human microbiota, can cause candidiasis under conditions of immunological imbalance, while C. neoformans, an environmental yeast, is notorious for causing cryptococcal meningitis, especially in individuals with HIV. Antifungal treatment is based on three classes of antifungals, however it is considered limited by problems of toxicity, resistance and availability of drugs. Thus, organoseleniums have demonstrated different pharmacological actions, among them antifungal such as ebselen. Recent studies have demonstrated the antifungal activity of Ebselen against various yeast species, including the genera Candida spp. and Cryptococcus spp., however, data regarding the fungicidal mechanism of action and virulence factors in these yeast are scarce.. Therefore, ebselen emerges as a promising candidate for combating fungal infecrions; however, its mechanism of action, particularly concerning the virulence factors of these yeasts, warrants further investigation. This study, therefore, aims to investigate the molecular mechanisms and cell death processes induced by this compound on Candida spp. and Cryptococcus spp. Additionally, it seeks to evaluate their efficacy in a murine model of cryptococcosis and to develop a gel for the treatment of vaginal candidiasis.