Study of extracellular vesicles from fungal pathogens with high impact on public health

• Grant number: 24/19475-3
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: February 24, 2025
• End date: April 12, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Samuel Goldenberg
• Grantee: Jean de Souza Lisboa Kozlowski
• Host Institution: Instituto Carlos Chagas. Fundação Oswaldo Cruz (Fiocruz). Ministério da Saúde (Brasil)

Abstract

Fungal infections cause high mortality rates worldwide. The Global Action Fund for Fungal Infections (GAFFI) reveals alarming data, indicating that more than 300 million people suffer annually from serious fungal infections, resulting in more than 1.5 million deaths, numbers comparable to diseases such as malaria and tuberculosis. Cancer patients are highly susceptible to fungal infections, directly impacting the costs of anti-tumor treatment. At the National Cancer Institute (INCA), spending on antifungal drugs such as amphotericin B exceeded 14 million reais between 2013 and 2016. According to the Centers for Disease Control and Prevention (CDC, USA), fungi are often associated with mortality from meningitis, with Cryptococcus spp causing around 200,000 deaths annually. In addition to the impact of Cryptococcus, Candida auris, an emerging fungus naturally resistant to antifungal drugs, is considered a global threat. In immunocompromised patients, its circulation in the bloodstream results in mortality rates ranging from 28% to 78%. An important aspect of the biology of these pathogenic fungi is the production of extracellular vesicles (EVs). EVs are now recognized as key players in cellular biology and in pathogen-host interactions. In fungi, although their existence has been known since 2007, their structure, content, and functions remain poorly understood. Historically, the study of fungal EVs has been based on established protocols for analyzing mammalian EVs, but there is no clarity on the best methods for analyzing these structures in fungi. Our recent data using alternative protocols revealed a remarkable diversity in fungal EVs, suggesting multiple biogenesis pathways. Since EVs have enormous potential as targets for developing antifungal drugs, vaccines, and diagnostic tools, we will use our experience in purifying and characterizing fungal EVs to study the structure, composition, and diversity of EVs produced by different pathogenic isolates of C. neoformans and C. auris. Understanding the composition of these pathogens' EVs could pave the way for understanding biogenesis and identifying therapeutic targets to combat severe fungal infections, reducing the negative impact on public health and the associated treatment costs. (AU)