Study of the role of secreted aspartyl protease (PbSAP) virulence of the pathogenic fungus Paracoccidioides brasiliensis

• Grant number: 14/08987-1
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2014
• Effective date (End): March 31, 2018
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Wagner Luiz Batista
• Grantee: Daniele Gonçalves Castilho
• Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Paracoccidioides brasiliensis is a thermodimorphic fungus and the etiological agent of paracoccidioidomycosis (PCM). The fungus infection is by inhalation of conidia present in the environment. For the development of the disease is essential that the conidia lodged in the pulmonary alveoli pass for the yeast phase, and this event was dependent on the temperature increase. The development of the disease depends on factors associated with the host's immune response and characteristics of the infectious agent, especially virulence. Some components were identified as potential factors involved in the virulence of P. brasiliensis and parasite/ host interaction, but few molecules involved in pathogenesis of the fungus were described. Quantitative proteomics studies performed in our laboratory using isolated Pb18 with different degrees of virulence showed differences in protein content between these isolates and the differentially expressed proteins found in isolated virulent Pb18 showed up as potential virulence factors. Among the proteins with increased expression highlights the vacuolar protease A, also known as the secreted aspartyl protease - PbSAP of P. lutzii (formerly known as Pb01). The expression of this protein was shown to be 7.1 times higher in isolated virulent Pb18 when compared to attenuated Pb18. The secreted aspartyl proteases are described as having an important role in many pathogenic fungal infections. In this sense, the study of this secreted protein may help understand the mechanisms of infection of P. brasiliensis. Thus, this project aims to investigate the role of PbSAP virulence of P. brasiliensis (isolate Pb18). Thus, the gene silencing PbSAP will be conducted through the antisense RNA technology associated with transformation mediated by Agrobacterium tumefaciens. This study may contribute significantly to understanding the role of this protease in the pathogenesis of PCM, allowing the identification of new therapeutic target and biomarker same virulence in this important systemic mycosis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CASTILHO, DANIELE GONCALVES; ALENCAR CHAVES, ALISON FELIPE; NAVARRO, MARINA VALENTE; CONCEICAO, PALLOMA MENDES; FERREIRA, KAREN SPADARI; DA SILVA, LUIZ SEVERINO; XANDER, PATRICIA; BATISTA, WAGNER LUIZ. Secreted aspartyl proteinase (PbSap) contributes to the virulence of Paracoccidioides brasiliensis infection. PLoS Neglected Tropical Diseases, v. 12, n. 9 SEP 2018. Web of Science Citations: 1.

CASTILHO, DANIELE G.; NAVARRO, MARINA V.; CHAVES, ALISON F. A.; XANDER, PATRICIA; BATISTA, WAGNER L. Recovery of the Paracoccidioides brasiliensis virulence after animal passage promotes changes in the antioxidant repertoire of the fungus. FEMS Yeast Research, v. 18, n. 2 MAR 2018. Web of Science Citations: 0.