Role of secreted aspartyl protease (PbSAP) in virulence and dimorphism in the pathogenic fungus Paracoccidioides brasiliensis

• Grant number: 14/13961-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2014
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Wagner Luiz Batista
• Grantee: Wagner Luiz Batista
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Patricia Xander Batista

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

(8)

(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)

CHAVES, ALISON F. A.; NAVARRO, MARINA V.; CASTILHO, DANIELE G.; CALADO, JULIANA C. P.; CONCEICAO, PALLOMA M.; BATISTA, WAGNER L.. A conserved dimorphism-regulating histidine kinase controls the dimorphic switching in Paracoccidioides brasiliensis. FEMS Yeast Research, v. 16, n. 5, AUG 2016. (14/13961-1, 15/09727-6)

TASHIMA, ALEXANDRE KEIJI; CASTILHO, DANIELE GONCALVES; ALENCAR CHAVES, ALISON FELIPE; XANDER, PATRICIA; ZELANIS, ANDRE; BATISTA, WAGNER LUIZ. Data in support of quantitative proteomics to identify potential virulence regulators in Paracoccidioides brasiliensis isolates. DATA IN BRIEF, v. 5, p. 155-160, DEC 2015. (14/13961-1, 12/19321-9, 11/14392-2)

TORRECILHAS, ANA CLAUDIA; XANDER, PATRICIA; FERREIRA, KAREN SPADARI; BATISTA, WAGNER LUIZ. Alternative Host Models for Testing Anti-Protozoal or Antifungal Compounds and Fungal Infection. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 18, n. 4, p. 300-311, 2018. (14/13961-1)

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. (14/13961-1, 17/04592-0, 14/08987-1)

CAMPOS, JOAO HENRIQUE; SOARES, RODRIGO PEDRO; RIBEIRO, KLEBER; ANDRADE, ANDRE CRONEMBERGER; BATISTA, WAGNER LUIZ; TORRECILHAS, ANA CLAUDIA. Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases. CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2015. (14/13961-1)

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. (17/04592-0, 14/13961-1, 14/08987-1)

CHAVES, ALISON F. A.; CASTILHO, DANIELE G.; NAVARRO, MARINA V.; OLIVEIRA, ANA K.; SERRANO, SOLANGE M. T.; TASHIMA, ALEXANDRE K.; BATISTA, WAGNER L.. Phosphosite-specific regulation of the oxidative-stress response of Paracoccidioides brasiliensis: a shotgun phosphoproteomic analysis. Microbes and Infection, v. 19, n. 1, p. 34-46, JAN 2017. (14/13961-1, 11/14392-2, 13/07467-1, 12/19321-9, 12/17530-0)

CAMPOS, JOAO HENRIQUE; SOARES, RODRIGO PEDRO; RIBEIRO, KLEBER; ANDRADE, ANDRE CRONEMBERGER; BATISTA, WAGNER LUIZ; TORRECILHAS, ANA CLAUDIA. Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2015, p. 14-pg., 2015-01-01. (14/13961-1)