Secreted aspartyl proteinase (PbSap) contributes to the virulence of Paracoccidioides brasiliensis infection

Autor(es)

Castilho, Daniele Goncalves ^[1] ; Alencar Chaves, Alison Felipe ^[1] ; Navarro, Marina Valente ^[1] ; Conceicao, Palloma Mendes ^[2] ; Ferreira, Karen Spadari ^[2] ; da Silva, Luiz Severino ^[1] ; Xander, Patricia ^[2] ; Batista, Wagner Luiz ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Pharmaceut Sci, Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 12, n. 9 SEP 2018.
• Citações Web of Science: 1

Resumo

Paracoccidioidomycosis (PCM) is the most prevalent deep mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. Virulence factors are important fungal characteristics that support the development of disease. Aspartyl proteases (Saps) are virulence factors in many human fungal pathogens that play an important role in the host invasion process. We report here that immunization with recombinant Sap from Paracoccidioides brasiliensis (rPbSap) imparted a protective effect in an experimental PCM model. The rPbSap-immunized mice had decreased fungal loads, and their lung parenchyma were notably preserved. An aspartyl protease inhibitor (pepstatin A) significantly decreased pulmonary injury and reduced fungal loads in the lung. Additionally, we observed that pepstatin A enhanced the fungicidal and phagocytic profile of macrophages against P. brasiliensis. Furthermore, PbSAPexpression was highly altered by environmental conditions, including thermal stress, dimorphism switching and low pH. Hence, our data suggest that PbSap is an important virulence regulator in P. brasiliensis. (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: 14/13961-1 - Avaliação do papel da aspartil protease secretada (PbSAP) na virulência e no dimorfismo do fungo patogênico Paracoccidioides brasiliensis
• Beneficiário: Wagner Luiz Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/08987-1 - Estudo do papel da aspartil protease secretada (PbSAP) na virulência do fungo patogênico Paracoccidioides brasiliensis
• Beneficiário: Daniele Gonçalves Castilho
• Modalidade de apoio: Bolsas no Brasil - Doutorado