The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi

Autores
Maciel, Belen Jesus; Reigada, Chantal; Di Girolamo, Fabio Augusto; Rengifo Carrillo, Marcos Ramón; Pereira, Claudio Alejandro; Miranda, Mariana Reneé; Martínez Sayé, Melisa Soledad
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease, caused by the parasite Trypanosoma cruzi, affects 6 million peopleworldwide. Although the drugs benznidazole (BZN) and nifurtimox are availableto treat Chagas, they are not effective in the chronic phase when most patientsare diagnosed. Moreover, long-term regimen and severe side effects often leadto poor adherence and treatment abandonment. These problems highlight theurgent need to develop new therapies to treat this neglected disease. Given thatthe antifungal drug nystatin (NYS) affects arginine uptake in yeasts, and fluctuationson arginine availability through transport processes in T. cruzi can negatively affectits viability, in this work we evaluated the potential of NYS for drug repurposingagainst T. cruzi. NYS inhibited arginine uptake and presented trypanocidal effect inboth epimastigotes (IC50 0.17 μM) and trypomastigotes (IC50 4.90 μM). In addition,treatment of infected cells with NYS decreased the release of trypomastigotes withbetter efficacy than BZN (IC50s 4.83 μM and 8.60 μM, respectively) suggesting thatNYS affects the progression of the intracellular life cycle. Furthermore, we observeda synergistic effect both in isolated trypomastigotes and infected cells when NYSwas combined with BZN, which could enhance efficacy while improving treatmentsafety and adherence. As in yeasts, the mechanism of action of NYS in T. cruziinvolved the plasma membrane disruption, and membrane transport processes, likeamino acids and thymidine uptake, were affected prior to the disruption probablydue to NYS interaction with the membrane. Drug repurposing is a recommendedstrategy by the World Health Organization to develop new therapeutic alternativesfor neglected diseases. Our results indicate that NYS presents great potential tobe repurposed as a trypanocidal drug to fight T. cruzi.
Fil: Maciel, Belen Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Rengifo Carrillo, Marcos Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Materia
NYSTATIN
DRUG REPURPOSING
TRYPANOSOMA CRUZI
TRYPANOCIDAL COMPOUNDS
CHAGAS DISEASE
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:11336/291011
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/291011
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruziMaciel, Belen JesusReigada, ChantalDi Girolamo, Fabio AugustoRengifo Carrillo, Marcos RamónPereira, Claudio AlejandroMiranda, Mariana ReneéMartínez Sayé, Melisa SoledadNYSTATINDRUG REPURPOSINGTRYPANOSOMA CRUZITRYPANOCIDAL COMPOUNDSCHAGAS DISEASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas disease, caused by the parasite Trypanosoma cruzi, affects 6 million peopleworldwide. Although the drugs benznidazole (BZN) and nifurtimox are availableto treat Chagas, they are not effective in the chronic phase when most patientsare diagnosed. Moreover, long-term regimen and severe side effects often leadto poor adherence and treatment abandonment. These problems highlight theurgent need to develop new therapies to treat this neglected disease. Given thatthe antifungal drug nystatin (NYS) affects arginine uptake in yeasts, and fluctuationson arginine availability through transport processes in T. cruzi can negatively affectits viability, in this work we evaluated the potential of NYS for drug repurposingagainst T. cruzi. NYS inhibited arginine uptake and presented trypanocidal effect inboth epimastigotes (IC50 0.17 μM) and trypomastigotes (IC50 4.90 μM). In addition,treatment of infected cells with NYS decreased the release of trypomastigotes withbetter efficacy than BZN (IC50s 4.83 μM and 8.60 μM, respectively) suggesting thatNYS affects the progression of the intracellular life cycle. Furthermore, we observeda synergistic effect both in isolated trypomastigotes and infected cells when NYSwas combined with BZN, which could enhance efficacy while improving treatmentsafety and adherence. As in yeasts, the mechanism of action of NYS in T. cruziinvolved the plasma membrane disruption, and membrane transport processes, likeamino acids and thymidine uptake, were affected prior to the disruption probablydue to NYS interaction with the membrane. Drug repurposing is a recommendedstrategy by the World Health Organization to develop new therapeutic alternativesfor neglected diseases. Our results indicate that NYS presents great potential tobe repurposed as a trypanocidal drug to fight T. cruzi.Fil: Maciel, Belen Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Rengifo Carrillo, Marcos Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFrontiers Media2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/291011Maciel, Belen Jesus; Reigada, Chantal; Di Girolamo, Fabio Augusto; Rengifo Carrillo, Marcos Ramón; Pereira, Claudio Alejandro; et al.; The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi; Frontiers Media; Frontiers in Microbiology; 16; 3-2025; 1-91664-302XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2025.1539629/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2025.1539629info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:13:03Zoai:ri.conicet.gov.ar:11336/291011instacron: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:34982026-08-25 15:13:04.055CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
title The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
spellingShingle The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
Maciel, Belen Jesus
NYSTATIN
DRUG REPURPOSING
TRYPANOSOMA CRUZI
TRYPANOCIDAL COMPOUNDS
CHAGAS DISEASE
title_short The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
title_full The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
title_fullStr The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
title_full_unstemmed The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
title_sort The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi
dc.creator.none.fl_str_mv Maciel, Belen Jesus
Reigada, Chantal
Di Girolamo, Fabio Augusto
Rengifo Carrillo, Marcos Ramón
Pereira, Claudio Alejandro
Miranda, Mariana Reneé
Martínez Sayé, Melisa Soledad
author Maciel, Belen Jesus
author_facet Maciel, Belen Jesus
Reigada, Chantal
Di Girolamo, Fabio Augusto
Rengifo Carrillo, Marcos Ramón
Pereira, Claudio Alejandro
Miranda, Mariana Reneé
Martínez Sayé, Melisa Soledad
author_role author
author2 Reigada, Chantal
Di Girolamo, Fabio Augusto
Rengifo Carrillo, Marcos Ramón
Pereira, Claudio Alejandro
Miranda, Mariana Reneé
Martínez Sayé, Melisa Soledad
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv NYSTATIN
DRUG REPURPOSING
TRYPANOSOMA CRUZI
TRYPANOCIDAL COMPOUNDS
CHAGAS DISEASE
topic NYSTATIN
DRUG REPURPOSING
TRYPANOSOMA CRUZI
TRYPANOCIDAL COMPOUNDS
CHAGAS DISEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease, caused by the parasite Trypanosoma cruzi, affects 6 million peopleworldwide. Although the drugs benznidazole (BZN) and nifurtimox are availableto treat Chagas, they are not effective in the chronic phase when most patientsare diagnosed. Moreover, long-term regimen and severe side effects often leadto poor adherence and treatment abandonment. These problems highlight theurgent need to develop new therapies to treat this neglected disease. Given thatthe antifungal drug nystatin (NYS) affects arginine uptake in yeasts, and fluctuationson arginine availability through transport processes in T. cruzi can negatively affectits viability, in this work we evaluated the potential of NYS for drug repurposingagainst T. cruzi. NYS inhibited arginine uptake and presented trypanocidal effect inboth epimastigotes (IC50 0.17 μM) and trypomastigotes (IC50 4.90 μM). In addition,treatment of infected cells with NYS decreased the release of trypomastigotes withbetter efficacy than BZN (IC50s 4.83 μM and 8.60 μM, respectively) suggesting thatNYS affects the progression of the intracellular life cycle. Furthermore, we observeda synergistic effect both in isolated trypomastigotes and infected cells when NYSwas combined with BZN, which could enhance efficacy while improving treatmentsafety and adherence. As in yeasts, the mechanism of action of NYS in T. cruziinvolved the plasma membrane disruption, and membrane transport processes, likeamino acids and thymidine uptake, were affected prior to the disruption probablydue to NYS interaction with the membrane. Drug repurposing is a recommendedstrategy by the World Health Organization to develop new therapeutic alternativesfor neglected diseases. Our results indicate that NYS presents great potential tobe repurposed as a trypanocidal drug to fight T. cruzi.
Fil: Maciel, Belen Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Rengifo Carrillo, Marcos Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
description Chagas disease, caused by the parasite Trypanosoma cruzi, affects 6 million peopleworldwide. Although the drugs benznidazole (BZN) and nifurtimox are availableto treat Chagas, they are not effective in the chronic phase when most patientsare diagnosed. Moreover, long-term regimen and severe side effects often leadto poor adherence and treatment abandonment. These problems highlight theurgent need to develop new therapies to treat this neglected disease. Given thatthe antifungal drug nystatin (NYS) affects arginine uptake in yeasts, and fluctuationson arginine availability through transport processes in T. cruzi can negatively affectits viability, in this work we evaluated the potential of NYS for drug repurposingagainst T. cruzi. NYS inhibited arginine uptake and presented trypanocidal effect inboth epimastigotes (IC50 0.17 μM) and trypomastigotes (IC50 4.90 μM). In addition,treatment of infected cells with NYS decreased the release of trypomastigotes withbetter efficacy than BZN (IC50s 4.83 μM and 8.60 μM, respectively) suggesting thatNYS affects the progression of the intracellular life cycle. Furthermore, we observeda synergistic effect both in isolated trypomastigotes and infected cells when NYSwas combined with BZN, which could enhance efficacy while improving treatmentsafety and adherence. As in yeasts, the mechanism of action of NYS in T. cruziinvolved the plasma membrane disruption, and membrane transport processes, likeamino acids and thymidine uptake, were affected prior to the disruption probablydue to NYS interaction with the membrane. Drug repurposing is a recommendedstrategy by the World Health Organization to develop new therapeutic alternativesfor neglected diseases. Our results indicate that NYS presents great potential tobe repurposed as a trypanocidal drug to fight T. cruzi.
publishDate 2025
dc.date.none.fl_str_mv 2025-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/291011
Maciel, Belen Jesus; Reigada, Chantal; Di Girolamo, Fabio Augusto; Rengifo Carrillo, Marcos Ramón; Pereira, Claudio Alejandro; et al.; The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi; Frontiers Media; Frontiers in Microbiology; 16; 3-2025; 1-9
1664-302X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/291011
identifier_str_mv Maciel, Belen Jesus; Reigada, Chantal; Di Girolamo, Fabio Augusto; Rengifo Carrillo, Marcos Ramón; Pereira, Claudio Alejandro; et al.; The potential of the antifungal nystatin to be repurposed to fight the protozoan Trypanosoma cruzi; Frontiers Media; Frontiers in Microbiology; 16; 3-2025; 1-9
1664-302X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2025.1539629
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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