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Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum

Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of...

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Autores principales: Sussmann, Rodrigo A. C., Gabriel, Heloisa B., Ríos, Alejandro García, Menchaca Vega, Danielle S., Yamaguchi, Lydia F., Doménech-Carbó, Antonio, Cebrián-Torrejón, Gerardo, Kimura, Emilia A., Kato, Massuo J., Bofill Verdaguer, Ignasi, Crispim, Marcell, Katzin, Alejandro M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069557/
https://www.ncbi.nlm.nih.gov/pubmed/35531326
http://dx.doi.org/10.3389/fcimb.2022.869085
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author Sussmann, Rodrigo A. C.
Gabriel, Heloisa B.
Ríos, Alejandro García
Menchaca Vega, Danielle S.
Yamaguchi, Lydia F.
Doménech-Carbó, Antonio
Cebrián-Torrejón, Gerardo
Kimura, Emilia A.
Kato, Massuo J.
Bofill Verdaguer, Ignasi
Crispim, Marcell
Katzin, Alejandro M.
author_facet Sussmann, Rodrigo A. C.
Gabriel, Heloisa B.
Ríos, Alejandro García
Menchaca Vega, Danielle S.
Yamaguchi, Lydia F.
Doménech-Carbó, Antonio
Cebrián-Torrejón, Gerardo
Kimura, Emilia A.
Kato, Massuo J.
Bofill Verdaguer, Ignasi
Crispim, Marcell
Katzin, Alejandro M.
author_sort Sussmann, Rodrigo A. C.
collection PubMed
description Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of P. falciparum is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs.
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spelling pubmed-90695572022-05-05 Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum Sussmann, Rodrigo A. C. Gabriel, Heloisa B. Ríos, Alejandro García Menchaca Vega, Danielle S. Yamaguchi, Lydia F. Doménech-Carbó, Antonio Cebrián-Torrejón, Gerardo Kimura, Emilia A. Kato, Massuo J. Bofill Verdaguer, Ignasi Crispim, Marcell Katzin, Alejandro M. Front Cell Infect Microbiol Cellular and Infection Microbiology Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of P. falciparum is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs. Frontiers Media S.A. 2022-04-21 /pmc/articles/PMC9069557/ /pubmed/35531326 http://dx.doi.org/10.3389/fcimb.2022.869085 Text en Copyright © 2022 Sussmann, Gabriel, Ríos, Menchaca Vega, Yamaguchi, Doménech-Carbó, Cebrián-Torrejón, Kimura, Kato, Bofill Verdaguer, Crispim and Katzin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Sussmann, Rodrigo A. C.
Gabriel, Heloisa B.
Ríos, Alejandro García
Menchaca Vega, Danielle S.
Yamaguchi, Lydia F.
Doménech-Carbó, Antonio
Cebrián-Torrejón, Gerardo
Kimura, Emilia A.
Kato, Massuo J.
Bofill Verdaguer, Ignasi
Crispim, Marcell
Katzin, Alejandro M.
Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
title Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
title_full Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
title_fullStr Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
title_full_unstemmed Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
title_short Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
title_sort presence of phylloquinone in the intraerythrocytic stages of plasmodium falciparum
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069557/
https://www.ncbi.nlm.nih.gov/pubmed/35531326
http://dx.doi.org/10.3389/fcimb.2022.869085
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