Evaluation of the proteomic profile of the pathogenic fungus Paracoccidioides brasiliensis in response to acidic pH

• Grant number: 23/07427-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Wagner Luiz Batista
• Grantee: Reinaldo Souza Oliveira
• 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 fungal disease caused by organisms of the genus Paracoccidioides spp. PCM is a systemic, granulomatous mycosis that is endemic in Latin America, with Brazil having the highest number of cases. Infection occurs by inhaling conidia or fragments of hyphae present in the soil. These fungi present a process of dimorphism, in which they adapt to the tissues of infected hosts, changing from their mycelial form (infectious form) to a yeast form (pathogenic form). As a pathogen, the fungus is subjected to a variety of stress conditions, including the host's immune response, which involves the production of reactive nitrogen and oxygen species, heat stress due to temperature changes during the transition, pH changes in phagolysosomes and hypoxia within granulomas. Fungi mount efficient responses to altered extracellular pH. Our group showed that acidic pH induces robust expression of aspartic proteases from Paracoccidioides brasiliensis, known as virulence factors in other fungi. Furthermore, we also observed that P. brasiliensis cultured in acidic pH conditions induces melanin production, an important virulence factor that has been shown to protect the fungus from phagocytosis and the action of antifungal drugs. However, little is known about the adaptation mechanisms of P. brasiliensis to acidic pH. Thus, this project aims to evaluate the proteomic profile of the pathogenic fungus P. brasiliensis after cultivation in acidic pH. For this, fungus cultures will be carried out at different acidic pHs and in control conditions (pH 6.5) using the Pb18 isolate of P. brasiliensis. Total proteins will be extracted, digested with trypsin, and analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). This study should contribute to understanding the fungus's biology and its interaction with the host in response to acidic pH.