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Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection
Toxoplasmosis, caused by Toxoplasma gondii, is a major public concern owing to its neurotropic nature and high morbidity and mortality rates in immunocompromised patients and newborns. Current treatment for this disease is inefficient and produces side effects. Inflammatory mediators produced during...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329421/ https://www.ncbi.nlm.nih.gov/pubmed/34354963 http://dx.doi.org/10.3389/fcimb.2021.706618 |
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author | de Assis, Diego Rodney Rodrigues Pimentel, Pollyana Maria de Oliveira dos Reis, Pablo Victor Mendes Rabelo, Rayane Aparecida Nonato Vitor, Ricardo Wagner Almeida Cordeiro, Marta do Nascimento Felicori, Liza Figueiredo Olórtegui, Carlos Delfin Chávez Resende, Jarbas Magalhães Teixeira, Mauro Martins Borges, Márcia Helena de Lima, Maria Elena Pimenta, Adriano Monteiro de Castro Machado, Fabiana Simão |
author_facet | de Assis, Diego Rodney Rodrigues Pimentel, Pollyana Maria de Oliveira dos Reis, Pablo Victor Mendes Rabelo, Rayane Aparecida Nonato Vitor, Ricardo Wagner Almeida Cordeiro, Marta do Nascimento Felicori, Liza Figueiredo Olórtegui, Carlos Delfin Chávez Resende, Jarbas Magalhães Teixeira, Mauro Martins Borges, Márcia Helena de Lima, Maria Elena Pimenta, Adriano Monteiro de Castro Machado, Fabiana Simão |
author_sort | de Assis, Diego Rodney Rodrigues |
collection | PubMed |
description | Toxoplasmosis, caused by Toxoplasma gondii, is a major public concern owing to its neurotropic nature and high morbidity and mortality rates in immunocompromised patients and newborns. Current treatment for this disease is inefficient and produces side effects. Inflammatory mediators produced during T. gondii infection (e.g., cytokines and nitric oxide) are crucial in controlling parasite replication. In this context, Tityus serrulatus venom (TsV) induces the production of inflammatory mediators by immune cells. Thus, this study aimed to isolate and identify the components of TsV with potential anti-T. gondii activity. TsV was extracted from scorpions and lyophilized or loaded onto a column to obtain its fractions. TsV subfractions were obtained using chromatography, and its amino acid sequence was identified and applied to peptide design using bioinformatics tools. The C57BL/6 mice and their harvested macrophages were used to test the anti-Toxoplasma activity of TsV components and peptides. TsV and its fraction F6 attenuated the replication of tachyzoites in macrophages and induced nitric oxide and cytokine (IL-12, TNF, and IL-6) production by infected cells, without host cell toxicity. Moreover, Su6-B toxin, a subfraction of F6, demonstrated anti-T. gondii activity. The partially elucidated and characterized amino acid sequence of Sub6-B demonstrated 93% similarity with T. serrulatus 2 toxin (Ts2). Ts2 mimetic peptides (“Pep1,” “Pep2a,” and “Pep2b”) were designed and synthesized. Pep1 and Pep2a, but not Pep2b, reduced the replication of tachyzoites in macrophages. In vivo, treatment of T. gondii-infected mice with Pep1, Pep2a, or Pep2b decreased the number of cerebral cysts and did not induce hepatotoxicity in the animals. Taken together, our data show promising immunomodulatory and antiparasitic activity of TsV that could be explored and applied in future therapies for treating infectious parasitic diseases such as toxoplasmosis. |
format | Online Article Text |
id | pubmed-8329421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83294212021-08-04 Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection de Assis, Diego Rodney Rodrigues Pimentel, Pollyana Maria de Oliveira dos Reis, Pablo Victor Mendes Rabelo, Rayane Aparecida Nonato Vitor, Ricardo Wagner Almeida Cordeiro, Marta do Nascimento Felicori, Liza Figueiredo Olórtegui, Carlos Delfin Chávez Resende, Jarbas Magalhães Teixeira, Mauro Martins Borges, Márcia Helena de Lima, Maria Elena Pimenta, Adriano Monteiro de Castro Machado, Fabiana Simão Front Cell Infect Microbiol Cellular and Infection Microbiology Toxoplasmosis, caused by Toxoplasma gondii, is a major public concern owing to its neurotropic nature and high morbidity and mortality rates in immunocompromised patients and newborns. Current treatment for this disease is inefficient and produces side effects. Inflammatory mediators produced during T. gondii infection (e.g., cytokines and nitric oxide) are crucial in controlling parasite replication. In this context, Tityus serrulatus venom (TsV) induces the production of inflammatory mediators by immune cells. Thus, this study aimed to isolate and identify the components of TsV with potential anti-T. gondii activity. TsV was extracted from scorpions and lyophilized or loaded onto a column to obtain its fractions. TsV subfractions were obtained using chromatography, and its amino acid sequence was identified and applied to peptide design using bioinformatics tools. The C57BL/6 mice and their harvested macrophages were used to test the anti-Toxoplasma activity of TsV components and peptides. TsV and its fraction F6 attenuated the replication of tachyzoites in macrophages and induced nitric oxide and cytokine (IL-12, TNF, and IL-6) production by infected cells, without host cell toxicity. Moreover, Su6-B toxin, a subfraction of F6, demonstrated anti-T. gondii activity. The partially elucidated and characterized amino acid sequence of Sub6-B demonstrated 93% similarity with T. serrulatus 2 toxin (Ts2). Ts2 mimetic peptides (“Pep1,” “Pep2a,” and “Pep2b”) were designed and synthesized. Pep1 and Pep2a, but not Pep2b, reduced the replication of tachyzoites in macrophages. In vivo, treatment of T. gondii-infected mice with Pep1, Pep2a, or Pep2b decreased the number of cerebral cysts and did not induce hepatotoxicity in the animals. Taken together, our data show promising immunomodulatory and antiparasitic activity of TsV that could be explored and applied in future therapies for treating infectious parasitic diseases such as toxoplasmosis. Frontiers Media S.A. 2021-07-20 /pmc/articles/PMC8329421/ /pubmed/34354963 http://dx.doi.org/10.3389/fcimb.2021.706618 Text en Copyright © 2021 de Assis, Pimentel, dos Reis, Rabelo, Vitor, Cordeiro, Felicori, Olórtegui, Resende, Teixeira, Borges, de Lima, Pimenta and Machado https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology de Assis, Diego Rodney Rodrigues Pimentel, Pollyana Maria de Oliveira dos Reis, Pablo Victor Mendes Rabelo, Rayane Aparecida Nonato Vitor, Ricardo Wagner Almeida Cordeiro, Marta do Nascimento Felicori, Liza Figueiredo Olórtegui, Carlos Delfin Chávez Resende, Jarbas Magalhães Teixeira, Mauro Martins Borges, Márcia Helena de Lima, Maria Elena Pimenta, Adriano Monteiro de Castro Machado, Fabiana Simão Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection |
title |
Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection |
title_full |
Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection |
title_fullStr |
Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection |
title_full_unstemmed |
Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection |
title_short |
Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection |
title_sort | tityus serrulatus (scorpion): from the crude venom to the construction of synthetic peptides and their possible therapeutic application against toxoplasma gondii infection |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329421/ https://www.ncbi.nlm.nih.gov/pubmed/34354963 http://dx.doi.org/10.3389/fcimb.2021.706618 |
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