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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 12, n. 9 SEP 2018.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 17/04592-0 - Evaluation of S-nitrosylated proteins of the Paracoccidioides brasiliensis after nitrosative stress and identification of potential redox signaling pathways
• Grantee: Wagner Luiz Batista
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/13961-1 - Role of secreted aspartyl protease (PbSAP) in virulence and dimorphism in the pathogenic fungus Paracoccidioides brasiliensis
• Grantee: Wagner Luiz Batista
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/08987-1 - Study of the role of secreted aspartyl protease (PbSAP) virulence of the pathogenic fungus Paracoccidioides brasiliensis
• Grantee: Daniele Gonçalves Castilho
• Support Opportunities: Scholarships in Brazil - Doctorate