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Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi

BACKGROUND: Chagas disease is the third most important neglected tropical disease. There is no vaccine available, and only two drugs are generally prescribed for the treatment, both of which with a wide range of side effects. Our study of T. cruzi PHBs revealed a pleiotropic function in different st...

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Autores principales: Ibarrola-Vannucci, Ana K., De Pablos, Luis M., Retana-Moreira, Lissette, Cornet-Gomez, Alberto, Cruz-Bustos, Teresa, Schijman, Alejandro G., Ramírez, José L., Vílchez, Susana, Osuna, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057595/
https://www.ncbi.nlm.nih.gov/pubmed/33830991
http://dx.doi.org/10.1371/journal.pntd.0009322
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author Ibarrola-Vannucci, Ana K.
De Pablos, Luis M.
Retana-Moreira, Lissette
Cornet-Gomez, Alberto
Cruz-Bustos, Teresa
Schijman, Alejandro G.
Ramírez, José L.
Vílchez, Susana
Osuna, Antonio
author_facet Ibarrola-Vannucci, Ana K.
De Pablos, Luis M.
Retana-Moreira, Lissette
Cornet-Gomez, Alberto
Cruz-Bustos, Teresa
Schijman, Alejandro G.
Ramírez, José L.
Vílchez, Susana
Osuna, Antonio
author_sort Ibarrola-Vannucci, Ana K.
collection PubMed
description BACKGROUND: Chagas disease is the third most important neglected tropical disease. There is no vaccine available, and only two drugs are generally prescribed for the treatment, both of which with a wide range of side effects. Our study of T. cruzi PHBs revealed a pleiotropic function in different stages of the parasite, participating actively in the transformation of the non-infective replicative epimastigote form into metacyclic trypomastigotes and also in the multiplication of intracellular amastigotes. METHODOLOGY/PRINCIPAL FINDINGS: To obtain and confirm our results, we applied several tools and techniques such as electron microscopy, immuno-electron microscopy, bioinformatics analysis and molecular biology. We transfected T. cruzi clones with the PHB genes, in order to overexpress the proteins and performed a CRISPR/Cas9 disruption to obtain partially silenced PHB1 parasites or completely silenced PHB2 parasites. The function of these proteins was also studied in the biology of the parasite, specifically in the transformation rate from non-infective forms to the metacyclic infective forms, and in their capacity of intracellular multiplication. CONCLUSION/SIGNIFICANCE: This research expands our understanding of the functions of PHBs in the life cycle of the parasite. It also highlights the protective role of prohibitins against ROS and reveals that the absence of PHB2 has a lethal effect on the parasite, a fact that could support the consideration of this protein as a possible target for therapeutic action.
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spelling pubmed-80575952021-05-04 Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi Ibarrola-Vannucci, Ana K. De Pablos, Luis M. Retana-Moreira, Lissette Cornet-Gomez, Alberto Cruz-Bustos, Teresa Schijman, Alejandro G. Ramírez, José L. Vílchez, Susana Osuna, Antonio PLoS Negl Trop Dis Research Article BACKGROUND: Chagas disease is the third most important neglected tropical disease. There is no vaccine available, and only two drugs are generally prescribed for the treatment, both of which with a wide range of side effects. Our study of T. cruzi PHBs revealed a pleiotropic function in different stages of the parasite, participating actively in the transformation of the non-infective replicative epimastigote form into metacyclic trypomastigotes and also in the multiplication of intracellular amastigotes. METHODOLOGY/PRINCIPAL FINDINGS: To obtain and confirm our results, we applied several tools and techniques such as electron microscopy, immuno-electron microscopy, bioinformatics analysis and molecular biology. We transfected T. cruzi clones with the PHB genes, in order to overexpress the proteins and performed a CRISPR/Cas9 disruption to obtain partially silenced PHB1 parasites or completely silenced PHB2 parasites. The function of these proteins was also studied in the biology of the parasite, specifically in the transformation rate from non-infective forms to the metacyclic infective forms, and in their capacity of intracellular multiplication. CONCLUSION/SIGNIFICANCE: This research expands our understanding of the functions of PHBs in the life cycle of the parasite. It also highlights the protective role of prohibitins against ROS and reveals that the absence of PHB2 has a lethal effect on the parasite, a fact that could support the consideration of this protein as a possible target for therapeutic action. Public Library of Science 2021-04-08 /pmc/articles/PMC8057595/ /pubmed/33830991 http://dx.doi.org/10.1371/journal.pntd.0009322 Text en © 2021 Ibarrola-Vannucci et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ibarrola-Vannucci, Ana K.
De Pablos, Luis M.
Retana-Moreira, Lissette
Cornet-Gomez, Alberto
Cruz-Bustos, Teresa
Schijman, Alejandro G.
Ramírez, José L.
Vílchez, Susana
Osuna, Antonio
Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi
title Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi
title_full Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi
title_fullStr Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi
title_full_unstemmed Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi
title_short Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi
title_sort characterization and functional analysis of the proteins prohibitin 1 and 2 in trypanosoma cruzi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057595/
https://www.ncbi.nlm.nih.gov/pubmed/33830991
http://dx.doi.org/10.1371/journal.pntd.0009322
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