Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism

Autor(es)

Silva, Rafael de Souza ; Segura, Wilson Dias ; Oliveira, Reinaldo Souza ; Xander, Patricia ; Batista, Wagner Luiz

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF FUNGI; v. 9, n. 3, p. 19-pg., 2023-03-01.

Resumo

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. The infection begins after inhalation of the fungal propagules and their thermo-dimorphic shift to yeast form. Proteases play an important role in the host invasion process and immune modulation in many pathogenic microorganisms. Aspartyl proteases are virulence factors in many human fungal pathogens that play an important role in the host invasion process morphogenesis, cellular function, immunity, and nutrition. In the present study, we characterized the modulation of acid proteases from Paracoccidioides brasiliensis. We detected four aspartyl proteases in P. brasiliensis with high homology to aspartic protease from Saccharomyces cerevisiae Pep4. Furthermore, we demonstrated that Pepstatin A can inhibit dimorphic switching (mycelium -> yeast) in P. brasiliensis. In addition, these genes were modulated during thermo-dimorphism (M -> Y transition) in the presence or absence of carbon and nitrogen sources and during growth at pH 4 during 24 and 48 h. We also observed that P. brasiliensis increase the secretion of aspartic proteases when cultivated at pH 4, and these acid proteases cleave BSA, collagen, and hemoglobin. These data suggest that aspartyl proteases are modulated by environmental conditions and during fungal thermo-dimorphism. Thus, this work brings new possibilities for studying the role of aspartyl proteases in the host-pathogen relationship and P. brasiliensis biology. (AU)

• Processo FAPESP: 17/04592-0 - Avaliação das proteínas S-nitrosiladas do fungo Paracoccidioides brasiliensis após estresse nitrosativo e identificação de potenciais vias de sinalização redox
• Beneficiário: Wagner Luiz Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/14235-3 - Avaliação do papel da histidina quinase reguladora do dimorfismo (Drk1) na modulação da parede celular e na patogenicidade do fungo Paracoccidioides brasiliensis
• Beneficiário: Wagner Luiz Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular