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Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata

Bovine babesiosis is a tick-transmitted disease caused by intraerythrocytic protozoan parasites of the genus Babesia. Its main causative agents in the Americas are Babesia bigemina and Babesia bovis, while Babesia ovata affects cattle in Asia. All Babesia species secrete proteins stored in organelle...

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Autores principales: Mosqueda, Juan, Hernandez-Silva, Diego Josimar, Ueti, Massaro W., Cruz-Reséndiz, Adolfo, Marquez-Cervantez, Ricardo, Valdez-Espinoza, Uriel Mauricio, Dang-Trinh, Minh-Anh, Nguyen, Thu-Thuy, Camacho-Nuez, Minerva, Mercado-Uriostegui, Miguel Angel, Aguilar-Tipacamú, Gabriela, Ramos-Aragon, Juan Alberto, Hernandez-Ortiz, Ruben, Kawazu, Shin-ichiro, Igarashi, Ikuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051436/
https://www.ncbi.nlm.nih.gov/pubmed/36986418
http://dx.doi.org/10.3390/pathogens12030495
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author Mosqueda, Juan
Hernandez-Silva, Diego Josimar
Ueti, Massaro W.
Cruz-Reséndiz, Adolfo
Marquez-Cervantez, Ricardo
Valdez-Espinoza, Uriel Mauricio
Dang-Trinh, Minh-Anh
Nguyen, Thu-Thuy
Camacho-Nuez, Minerva
Mercado-Uriostegui, Miguel Angel
Aguilar-Tipacamú, Gabriela
Ramos-Aragon, Juan Alberto
Hernandez-Ortiz, Ruben
Kawazu, Shin-ichiro
Igarashi, Ikuo
author_facet Mosqueda, Juan
Hernandez-Silva, Diego Josimar
Ueti, Massaro W.
Cruz-Reséndiz, Adolfo
Marquez-Cervantez, Ricardo
Valdez-Espinoza, Uriel Mauricio
Dang-Trinh, Minh-Anh
Nguyen, Thu-Thuy
Camacho-Nuez, Minerva
Mercado-Uriostegui, Miguel Angel
Aguilar-Tipacamú, Gabriela
Ramos-Aragon, Juan Alberto
Hernandez-Ortiz, Ruben
Kawazu, Shin-ichiro
Igarashi, Ikuo
author_sort Mosqueda, Juan
collection PubMed
description Bovine babesiosis is a tick-transmitted disease caused by intraerythrocytic protozoan parasites of the genus Babesia. Its main causative agents in the Americas are Babesia bigemina and Babesia bovis, while Babesia ovata affects cattle in Asia. All Babesia species secrete proteins stored in organelles of the apical complex, which are involved in all steps of the invasion process of vertebrate host cells. Unlike other apicomplexans, which have dense granules, babesia parasites instead have large, round intracellular organelles called spherical bodies. Evidence suggests that proteins from these organelles are released during the process of invading red blood cells, where spherical body proteins (SBPs) play an important role in cytoskeleton reorganization. In this study, we characterized the gene that encodes SBP4 in B. bigemina. This gene is transcribed and expressed in the erythrocytic stages of B. bigemina. The sbp4 gene consists of 834 nucleotides without introns that encode a protein of 277 amino acids. In silico analysis predicted a signal peptide that is cleaved at residue 20, producing a 28.88-kDa protein. The presence of a signal peptide and the absence of transmembrane domains suggest that this protein is secreted. Importantly, when cattle were immunized with recombinant B. bigemina SBP4, antibodies identified B. bigemina and B. ovata merozoites according to confocal microscopy observations and were able to neutralize parasite multiplication in vitro for both species. Four peptides with predicted B-cell epitopes were identified to be conserved in 17 different isolates from six countries. Compared with the pre-immunization sera, antibodies against these conserved peptides reduced parasite invasion in vitro by 57%, 44%, 42%, and 38% for peptides 1, 2, 3, and 4, respectively (p < 0.05). Moreover, sera from cattle infected with B. bigemina cattle contained antibodies that recognized the individual peptides. All these results support the concept of spb4 as a new gene in B. bigemina that should be considered a candidate for a vaccine to control bovine babesiosis.
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spelling pubmed-100514362023-03-30 Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata Mosqueda, Juan Hernandez-Silva, Diego Josimar Ueti, Massaro W. Cruz-Reséndiz, Adolfo Marquez-Cervantez, Ricardo Valdez-Espinoza, Uriel Mauricio Dang-Trinh, Minh-Anh Nguyen, Thu-Thuy Camacho-Nuez, Minerva Mercado-Uriostegui, Miguel Angel Aguilar-Tipacamú, Gabriela Ramos-Aragon, Juan Alberto Hernandez-Ortiz, Ruben Kawazu, Shin-ichiro Igarashi, Ikuo Pathogens Article Bovine babesiosis is a tick-transmitted disease caused by intraerythrocytic protozoan parasites of the genus Babesia. Its main causative agents in the Americas are Babesia bigemina and Babesia bovis, while Babesia ovata affects cattle in Asia. All Babesia species secrete proteins stored in organelles of the apical complex, which are involved in all steps of the invasion process of vertebrate host cells. Unlike other apicomplexans, which have dense granules, babesia parasites instead have large, round intracellular organelles called spherical bodies. Evidence suggests that proteins from these organelles are released during the process of invading red blood cells, where spherical body proteins (SBPs) play an important role in cytoskeleton reorganization. In this study, we characterized the gene that encodes SBP4 in B. bigemina. This gene is transcribed and expressed in the erythrocytic stages of B. bigemina. The sbp4 gene consists of 834 nucleotides without introns that encode a protein of 277 amino acids. In silico analysis predicted a signal peptide that is cleaved at residue 20, producing a 28.88-kDa protein. The presence of a signal peptide and the absence of transmembrane domains suggest that this protein is secreted. Importantly, when cattle were immunized with recombinant B. bigemina SBP4, antibodies identified B. bigemina and B. ovata merozoites according to confocal microscopy observations and were able to neutralize parasite multiplication in vitro for both species. Four peptides with predicted B-cell epitopes were identified to be conserved in 17 different isolates from six countries. Compared with the pre-immunization sera, antibodies against these conserved peptides reduced parasite invasion in vitro by 57%, 44%, 42%, and 38% for peptides 1, 2, 3, and 4, respectively (p < 0.05). Moreover, sera from cattle infected with B. bigemina cattle contained antibodies that recognized the individual peptides. All these results support the concept of spb4 as a new gene in B. bigemina that should be considered a candidate for a vaccine to control bovine babesiosis. MDPI 2023-03-22 /pmc/articles/PMC10051436/ /pubmed/36986418 http://dx.doi.org/10.3390/pathogens12030495 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mosqueda, Juan
Hernandez-Silva, Diego Josimar
Ueti, Massaro W.
Cruz-Reséndiz, Adolfo
Marquez-Cervantez, Ricardo
Valdez-Espinoza, Uriel Mauricio
Dang-Trinh, Minh-Anh
Nguyen, Thu-Thuy
Camacho-Nuez, Minerva
Mercado-Uriostegui, Miguel Angel
Aguilar-Tipacamú, Gabriela
Ramos-Aragon, Juan Alberto
Hernandez-Ortiz, Ruben
Kawazu, Shin-ichiro
Igarashi, Ikuo
Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata
title Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata
title_full Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata
title_fullStr Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata
title_full_unstemmed Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata
title_short Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata
title_sort spherical body protein 4 from babesia bigemina: a novel gene that contains conserved b-cell epitopes and induces cross-reactive neutralizing antibodies in babesia ovata
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051436/
https://www.ncbi.nlm.nih.gov/pubmed/36986418
http://dx.doi.org/10.3390/pathogens12030495
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