Modulation of Melanization in Paracoccidioides brasiliensis Under Acidic and Copper-Supplemented Conditions: Impacts on the Response to Different Stresses

• Grant number: 24/18382-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Wagner Luiz Batista
• Grantee: Eduardo Correa Louvandini
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Paracoccidioidomycosis (PCM) is a granulomatous mycosis caused by fungi of the genus Paracoccidioides, belonging to the Ajellomycetaceae family. These fungi are thermodimorphic, meaning they undergo a transition from mycelium to yeast within the host. During infection, the fungus is exposed to various stress conditions, including drastic pH changes in the phagolysosome and hypoxic environments. In recent years, our research group has been investigating the response of P. brasiliensis to different types of stress. It was observed that this fungus exhibits high resistance to pH variations, showing melanization when exposed to acidic environments (pH 4.0) and increased expression of a copper transporter of the Ctr3 type. Melanin is considered an important virulence factor, as it is associated with increased resistance to oxidative stress and antifungal drugs, while copper acts as a cofactor for key enzymes in melanin synthesis. However, few studies have explored the impact of acidic environments and copper supplementation on the melanization of P. brasiliensis. This scientific initiation project aims to evaluate the effects of these conditions on fungal melanization, using proteomic analyses, gene expression related to melanin, assessment of melanization kinetics, production of reactive oxygen species (ROS), antioxidant enzyme activity, and P. brasiliensis viability and resistance under different stress conditions. The expected results may provide relevant insights into the adaptive mechanisms of the fungus in hostile environments and suggest new strategies for the development of antifungal therapies.