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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Schistosoma mansoni venom allergen-like protein 18 (SmVAL18) is a plasminogen-binding protein secreted during the early stages of mammalian-host infection

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Author(s):
Fernandes, Rafaela S. [1, 2] ; Fernandes, Luis G. V. [1, 2] ; de Godoy, Andre S. [3] ; Miyasato, Patricia A. [4] ; Nakano, Eliana [4] ; Farias, Leonardo P. [5] ; Nascimento, Ana L. T. O. [1] ; Leite, Luciana C. C. [1]
Total Authors: 8
Affiliation:
[1] Inst Butantan, Lab Desenvolvimento Vacinas, Av Vital Brasil, 1500, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Programa Posgrad Interunidades Biotecnol, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil
[4] Inst Butantan, Lab Parasitol, Av Vital Brasil, 1500, Sao Paulo, SP - Brazil
[5] IGM Fundacao, Oswaldo Cruz FIOCRUZ, Rua Waldemar Falcao, 121, BR-40296710 Salvador, BA - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Molecular and Biochemical Parasitology; v. 221, p. 23-31, APR 2018.
Web of Science Citations: 0
Abstract

Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma which have a complex life cycle characterized by an asexual multiplication phase in the snail intermediate host and a sexual reproduction phase in the mammalian definitive host. The initial steps of the human host infection involve the secretion of proteins contained in the acetabular glands of cercariae that promote parasite adhesion and proteolysis of the skin layers. Herein, we performed a functional analysis of SmVAL18, identified as one of the three SCP/TAPS proteins constituent of cercarial secretions. We evaluated the SmVAL18 binding to immobilized macromolecules of the extracellular matrix (ECM) and to plasma components. Recombinant protein, expressed in E. coli, was found to maintain an ordered secondary structure typical of the SCP/TAPS domain after purification. Expression of native SmVAL18 protein was verified to be restricted to cercariae and 3-h schistosomula stages; furthermore, the protein was observed in the corresponding secretions, confirming that SmVAL18 is secreted during the first 3 h of in vitro culture. rSmVAL18 was able to interact specifically with plasminogen (PLG) and enhance its conversion into plasmin in the presence of the urokinase-type plasminogen activator (uPA). Protein homology modelling suggested that the PLG-rSmVAL18 interaction was mediated by lysine residues of the protein. This was supported by in vitro data using the lysine analogue, 6-aminocaproic acid (ACA), which abolished the interaction. Finally, our results showed that both cercariae and 3-h schistosomula, as well as their corresponding secretions, exhibited the capacity to bind PLG and enhance its conversion into plasmin in vitro in the same way as observed for the recombinant protein. In conclusion, our findings show that SmVAL18 is a novel PLG-binding protein secreted during the early stages of the mammalian-host infection. (AU)

FAPESP's process: 12/23124-4 - Investigating the effector mechanisms of the Schistosoma mansoni attenuated vaccine by Systems Vaccinology
Grantee:Luciana Cezar de Cerqueira Leite
Support Opportunities: Regular Research Grants
FAPESP's process: 10/18486-9 - Molecular characterization and immunological evaluation of VAL (Venom Allergen-Like protein) protein family from Schistosoma mansoni
Grantee:Rafaela Sachetto Fernandes
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)