Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway

Autores
Simão Gurge, Raquel M.; Wunderlich, Gerhard; Cricco, Julia Alejandra; Cubillos, Eliana F. Galindo; Doménech Carbó, Antonio; Cebrián Torrejón, Gerardo; Almeida, Fernando G.; Cirulli, Brenda Analía; Katzin, Alejandro M.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the addition of these drugs. We conclude that heme O synthesis occurs in blood stage-P. falciparum and this pathway could be a potential target for antimalarial drugs.
Fil: Simão Gurge, Raquel M.. Universidade de Sao Paulo; Brasil
Fil: Wunderlich, Gerhard. Universidade de Sao Paulo; Brasil
Fil: Cricco, Julia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Cubillos, Eliana F. Galindo. Universidade de Sao Paulo; Brasil
Fil: Doménech Carbó, Antonio. Universidad de Valencia; España
Fil: Cebrián Torrejón, Gerardo. Université des Antilles; Francia. Universidad de Valencia; España
Fil: Almeida, Fernando G.. Universidade de Sao Paulo; Brasil
Fil: Cirulli, Brenda Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Katzin, Alejandro M.. Universidade de Sao Paulo; Brasil
Materia
PLAMODIUM FALCIPARUM
MALARIA
HEME O
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:11336/162477
Acceder
id CONICETDig_0a58606453ee864ed04abc52c3f87c43
oai_identifier_str oai:ri.conicet.gov.ar:11336/162477
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathwaySimão Gurge, Raquel M.Wunderlich, GerhardCricco, Julia AlejandraCubillos, Eliana F. GalindoDoménech Carbó, AntonioCebrián Torrejón, GerardoAlmeida, Fernando G.Cirulli, Brenda AnalíaKatzin, Alejandro M.PLAMODIUM FALCIPARUMMALARIAHEME Ohttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the addition of these drugs. We conclude that heme O synthesis occurs in blood stage-P. falciparum and this pathway could be a potential target for antimalarial drugs.Fil: Simão Gurge, Raquel M.. Universidade de Sao Paulo; BrasilFil: Wunderlich, Gerhard. Universidade de Sao Paulo; BrasilFil: Cricco, Julia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Cubillos, Eliana F. Galindo. Universidade de Sao Paulo; BrasilFil: Doménech Carbó, Antonio. Universidad de Valencia; EspañaFil: Cebrián Torrejón, Gerardo. Université des Antilles; Francia. Universidad de Valencia; EspañaFil: Almeida, Fernando G.. Universidade de Sao Paulo; BrasilFil: Cirulli, Brenda Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Katzin, Alejandro M.. Universidade de Sao Paulo; BrasilNature Research2019-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162477Simão Gurge, Raquel M.; Wunderlich, Gerhard; Cricco, Julia Alejandra; Cubillos, Eliana F. Galindo; Doménech Carbó, Antonio; et al.; Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway; Nature Research; Scientific Reports; 9; 1; 12-2019; 1-132045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-55506-yinfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-019-55506-yinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:27:01Zoai:ri.conicet.gov.ar:11336/162477instacron: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:34982025-10-15 14:27:01.563CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
title Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
spellingShingle Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
Simão Gurge, Raquel M.
PLAMODIUM FALCIPARUM
MALARIA
HEME O
title_short Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
title_full Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
title_fullStr Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
title_full_unstemmed Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
title_sort Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
dc.creator.none.fl_str_mv Simão Gurge, Raquel M.
Wunderlich, Gerhard
Cricco, Julia Alejandra
Cubillos, Eliana F. Galindo
Doménech Carbó, Antonio
Cebrián Torrejón, Gerardo
Almeida, Fernando G.
Cirulli, Brenda Analía
Katzin, Alejandro M.
author Simão Gurge, Raquel M.
author_facet Simão Gurge, Raquel M.
Wunderlich, Gerhard
Cricco, Julia Alejandra
Cubillos, Eliana F. Galindo
Doménech Carbó, Antonio
Cebrián Torrejón, Gerardo
Almeida, Fernando G.
Cirulli, Brenda Analía
Katzin, Alejandro M.
author_role author
author2 Wunderlich, Gerhard
Cricco, Julia Alejandra
Cubillos, Eliana F. Galindo
Doménech Carbó, Antonio
Cebrián Torrejón, Gerardo
Almeida, Fernando G.
Cirulli, Brenda Analía
Katzin, Alejandro M.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PLAMODIUM FALCIPARUM
MALARIA
HEME O
topic PLAMODIUM FALCIPARUM
MALARIA
HEME O
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the addition of these drugs. We conclude that heme O synthesis occurs in blood stage-P. falciparum and this pathway could be a potential target for antimalarial drugs.
Fil: Simão Gurge, Raquel M.. Universidade de Sao Paulo; Brasil
Fil: Wunderlich, Gerhard. Universidade de Sao Paulo; Brasil
Fil: Cricco, Julia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Cubillos, Eliana F. Galindo. Universidade de Sao Paulo; Brasil
Fil: Doménech Carbó, Antonio. Universidad de Valencia; España
Fil: Cebrián Torrejón, Gerardo. Université des Antilles; Francia. Universidad de Valencia; España
Fil: Almeida, Fernando G.. Universidade de Sao Paulo; Brasil
Fil: Cirulli, Brenda Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Katzin, Alejandro M.. Universidade de Sao Paulo; Brasil
description A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the addition of these drugs. We conclude that heme O synthesis occurs in blood stage-P. falciparum and this pathway could be a potential target for antimalarial drugs.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
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/11336/162477
Simão Gurge, Raquel M.; Wunderlich, Gerhard; Cricco, Julia Alejandra; Cubillos, Eliana F. Galindo; Doménech Carbó, Antonio; et al.; Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway; Nature Research; Scientific Reports; 9; 1; 12-2019; 1-13
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162477
identifier_str_mv Simão Gurge, Raquel M.; Wunderlich, Gerhard; Cricco, Julia Alejandra; Cubillos, Eliana F. Galindo; Doménech Carbó, Antonio; et al.; Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway; Nature Research; Scientific Reports; 9; 1; 12-2019; 1-13
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-55506-y
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-019-55506-y
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082722172239872
score 13.22299

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