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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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