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https://www.arca.fiocruz.br/handle/icict/68522
EVALUATION OF SYNTHETIC PEPTIDES FROM SCHISTOSOMA MANSONI ATP DIPHOSPHOHYDROLASE 1: IN SILICO APPROACHES FOR CHARACTERIZATION AND PROSPECTIVE APPLICATION IN DIAGNOSIS OF SCHISTOSOMIASIS
Author
Affilliation
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Instituto Butantan. Laboratório de Toxinologia Aplicada. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Diagnóstico e Terapia de Doenças Infecciosas e Câncer. Belo Horizonte, MG, Brasil.
Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Biofísica. São Paulo, SP, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Instituto Butantan. Laboratório de Toxinologia Aplicada. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Diagnóstico e Terapia de Doenças Infecciosas e Câncer. Belo Horizonte, MG, Brasil.
Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Biofísica. São Paulo, SP, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Instituto de Ciências Biológicas. Juiz de Fora, MG, Brasil.
Abstract
Schistosomiasis is the infection caused by Schistosoma mansoni and constitutes a worldwide public health problem. The parasitological recommended method and serological methods can be used for the detection of eggs and antibodies, respectively. However, both have limitations, especially in low endemicity areas. Thus, new approaches for the diagnosis of schistosomiasis are essential. In this study, a six-amino acid peptide and derived sequences from SmATPDase1 were synthesized for the evaluation of immunogenicity. SmATPDase1 is included in a protein group in S. mansoni tegument; therefore, its peptides could be potential candidates for diagnostic antigens. In the hypothetical SmATPDase1 three-dimensional structure, peptides are located in a region exposed and accessible to antibody binding. In addition, peptide amino acid sequences are conserved in the most relevant Schistosoma species and have low identity with human NTPDases isoforms. Swiss mice immunization resulted in significant anti-peptide polyclonal antibodies production, which recognized a 63 kDa protein in tegument and adult worm preparations. By immunofluorescence microscopy, polyclonal antibodies also identified this enzyme in cercariae. Sera of infected animals presented high seropositivity in ELISA-peptides, with an area under curve (AUC) greater than 0.96 for all peptides. In mice with low parasite burden, we observed a seropositivity AUC > 0.9. Reactivity in the prepatent period exhibited AUC values greater than 0.94 for all peptides. Anti-P1425 monoclonal antibodies were successfully produced, and mAbs recognized the integral protein in ELISA and Western blots. The data indicate that peptides from SmATPDase1 are potential biomarkers for schistosomiasis, and anti-peptide antibodies are interesting tools for the detection of the infection.
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