Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form

Autores
Prego, Alejo Facundo; Alonso, Guillermo Daniel
Año de publicación
2023
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Trypanosoma cruzi has a complex life cycle, alternating between an insect vector and the human host, with three well-defined stages: epimastigotes, trypomastigotes, and amastigotes. The stages present in humans are bloodstream trypomastigotes, which is the infective but non-replicative form, and amastigotes, the intracellular replicative form, which are the focus of clinical treatments. Currently, there are two drugs used for treatment: benznidazole (Bz) and nifurtimox. These drugs must be metabolized by the parasite, so they can have an effect, and have a high degree of toxicity to the patient, often leading to treatment abandonment. Recently, the presence of dormant amastigotes within infected cells was described, and they are considered one of the possible causes of therapeutic failure due to their low or null metabolic activity, being able to resist Bz treatment, redifferentiate into trypomastigotes, and reinfect, causing disease relapse. Previous studies described a strategy to differentiate trypomastigotes into amastigotes axenically, using an acidic medium, and maintaining them in this state for a short period (10 days). In this study, we describe a new formulation that allows doubling the cultivation time of axenic amastigotes while preserving their ability to differentiate into trypomastigotes and maintaining their infective potential, similar behavior as dormants. Additionally, we observed signs of a more active metabolism in amastigotes obtained from infected Vero cell cultures, as opposed to those obtained through in vitro differentiation. Therefore, it is necessary to expand studies to determine whether using axenic amastigotes as a model for cultured amastigotes is equivalent or if they would exhibit reduced metabolic activity, making them more similar to dormants.
Fil: Prego, Alejo Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
XXXIV Reunión anual de la Sociedad Argentina de Protozoología
La Plata
Argentina
Sociedad Argentina de Protozoología
Materia
DIFERENCIACIÓN CELULAR
AMASTIGOGÉNESIS
METABOLISMO
ENFERMEDAD DE CHAGAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/242147

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spelling Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite formPrego, Alejo FacundoAlonso, Guillermo DanielDIFERENCIACIÓN CELULARAMASTIGOGÉNESISMETABOLISMOENFERMEDAD DE CHAGAShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma cruzi has a complex life cycle, alternating between an insect vector and the human host, with three well-defined stages: epimastigotes, trypomastigotes, and amastigotes. The stages present in humans are bloodstream trypomastigotes, which is the infective but non-replicative form, and amastigotes, the intracellular replicative form, which are the focus of clinical treatments. Currently, there are two drugs used for treatment: benznidazole (Bz) and nifurtimox. These drugs must be metabolized by the parasite, so they can have an effect, and have a high degree of toxicity to the patient, often leading to treatment abandonment. Recently, the presence of dormant amastigotes within infected cells was described, and they are considered one of the possible causes of therapeutic failure due to their low or null metabolic activity, being able to resist Bz treatment, redifferentiate into trypomastigotes, and reinfect, causing disease relapse. Previous studies described a strategy to differentiate trypomastigotes into amastigotes axenically, using an acidic medium, and maintaining them in this state for a short period (10 days). In this study, we describe a new formulation that allows doubling the cultivation time of axenic amastigotes while preserving their ability to differentiate into trypomastigotes and maintaining their infective potential, similar behavior as dormants. Additionally, we observed signs of a more active metabolism in amastigotes obtained from infected Vero cell cultures, as opposed to those obtained through in vitro differentiation. Therefore, it is necessary to expand studies to determine whether using axenic amastigotes as a model for cultured amastigotes is equivalent or if they would exhibit reduced metabolic activity, making them more similar to dormants.Fil: Prego, Alejo Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaXXXIV Reunión anual de la Sociedad Argentina de ProtozoologíaLa PlataArgentinaSociedad Argentina de ProtozoologíaSociedad Argentina de Protozoología2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/242147Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form; XXXIV Reunión anual de la Sociedad Argentina de Protozoología; La Plata; Argentina; 2023; 79-802953-5751CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://protozoologia.org.ar/wp-content/uploads/PARASITUS-Volumen-2-2023-ISSN-2953-5751.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:00:53Zoai:ri.conicet.gov.ar:11336/242147instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:00:54.016CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
title Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
spellingShingle Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
Prego, Alejo Facundo
DIFERENCIACIÓN CELULAR
AMASTIGOGÉNESIS
METABOLISMO
ENFERMEDAD DE CHAGAS
title_short Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
title_full Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
title_fullStr Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
title_full_unstemmed Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
title_sort Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form
dc.creator.none.fl_str_mv Prego, Alejo Facundo
Alonso, Guillermo Daniel
author Prego, Alejo Facundo
author_facet Prego, Alejo Facundo
Alonso, Guillermo Daniel
author_role author
author2 Alonso, Guillermo Daniel
author2_role author
dc.subject.none.fl_str_mv DIFERENCIACIÓN CELULAR
AMASTIGOGÉNESIS
METABOLISMO
ENFERMEDAD DE CHAGAS
topic DIFERENCIACIÓN CELULAR
AMASTIGOGÉNESIS
METABOLISMO
ENFERMEDAD DE CHAGAS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma cruzi has a complex life cycle, alternating between an insect vector and the human host, with three well-defined stages: epimastigotes, trypomastigotes, and amastigotes. The stages present in humans are bloodstream trypomastigotes, which is the infective but non-replicative form, and amastigotes, the intracellular replicative form, which are the focus of clinical treatments. Currently, there are two drugs used for treatment: benznidazole (Bz) and nifurtimox. These drugs must be metabolized by the parasite, so they can have an effect, and have a high degree of toxicity to the patient, often leading to treatment abandonment. Recently, the presence of dormant amastigotes within infected cells was described, and they are considered one of the possible causes of therapeutic failure due to their low or null metabolic activity, being able to resist Bz treatment, redifferentiate into trypomastigotes, and reinfect, causing disease relapse. Previous studies described a strategy to differentiate trypomastigotes into amastigotes axenically, using an acidic medium, and maintaining them in this state for a short period (10 days). In this study, we describe a new formulation that allows doubling the cultivation time of axenic amastigotes while preserving their ability to differentiate into trypomastigotes and maintaining their infective potential, similar behavior as dormants. Additionally, we observed signs of a more active metabolism in amastigotes obtained from infected Vero cell cultures, as opposed to those obtained through in vitro differentiation. Therefore, it is necessary to expand studies to determine whether using axenic amastigotes as a model for cultured amastigotes is equivalent or if they would exhibit reduced metabolic activity, making them more similar to dormants.
Fil: Prego, Alejo Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
XXXIV Reunión anual de la Sociedad Argentina de Protozoología
La Plata
Argentina
Sociedad Argentina de Protozoología
description Trypanosoma cruzi has a complex life cycle, alternating between an insect vector and the human host, with three well-defined stages: epimastigotes, trypomastigotes, and amastigotes. The stages present in humans are bloodstream trypomastigotes, which is the infective but non-replicative form, and amastigotes, the intracellular replicative form, which are the focus of clinical treatments. Currently, there are two drugs used for treatment: benznidazole (Bz) and nifurtimox. These drugs must be metabolized by the parasite, so they can have an effect, and have a high degree of toxicity to the patient, often leading to treatment abandonment. Recently, the presence of dormant amastigotes within infected cells was described, and they are considered one of the possible causes of therapeutic failure due to their low or null metabolic activity, being able to resist Bz treatment, redifferentiate into trypomastigotes, and reinfect, causing disease relapse. Previous studies described a strategy to differentiate trypomastigotes into amastigotes axenically, using an acidic medium, and maintaining them in this state for a short period (10 days). In this study, we describe a new formulation that allows doubling the cultivation time of axenic amastigotes while preserving their ability to differentiate into trypomastigotes and maintaining their infective potential, similar behavior as dormants. Additionally, we observed signs of a more active metabolism in amastigotes obtained from infected Vero cell cultures, as opposed to those obtained through in vitro differentiation. Therefore, it is necessary to expand studies to determine whether using axenic amastigotes as a model for cultured amastigotes is equivalent or if they would exhibit reduced metabolic activity, making them more similar to dormants.
publishDate 2023
dc.date.none.fl_str_mv 2023
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/242147
Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form; XXXIV Reunión anual de la Sociedad Argentina de Protozoología; La Plata; Argentina; 2023; 79-80
2953-5751
CONICET Digital
CONICET
url http://hdl.handle.net/11336/242147
identifier_str_mv Axenic culture of Trypanosoma cruzi amastigotes as a model for differential metabolic characteristics in the intracellular parasite form; XXXIV Reunión anual de la Sociedad Argentina de Protozoología; La Plata; Argentina; 2023; 79-80
2953-5751
CONICET Digital
CONICET
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