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Plasmodium falciparum: multifaceted resistance to artemisinins
Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to paras...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784301/ https://www.ncbi.nlm.nih.gov/pubmed/26955948 http://dx.doi.org/10.1186/s12936-016-1206-9 |
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author | Paloque, Lucie Ramadani, Arba P. Mercereau-Puijalon, Odile Augereau, Jean-Michel Benoit-Vical, Françoise |
author_facet | Paloque, Lucie Ramadani, Arba P. Mercereau-Puijalon, Odile Augereau, Jean-Michel Benoit-Vical, Françoise |
author_sort | Paloque, Lucie |
collection | PubMed |
description | Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. The enhanced P. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage and an altered cell cycle gene regulation within a complex network involving the unfolded protein response, the PI3K/PI3P/AKT pathway, the PfPK4/eIF2α cascade and yet unidentified transcription factor(s), with minimal energetic requirements and fatty acid metabolism maintained in the mitochondrion and apicoplast. The detailed study of these mechanisms offers a way forward for identifying future intervention targets to fend off established artemisinin resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-016-1206-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4784301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47843012016-03-10 Plasmodium falciparum: multifaceted resistance to artemisinins Paloque, Lucie Ramadani, Arba P. Mercereau-Puijalon, Odile Augereau, Jean-Michel Benoit-Vical, Françoise Malar J Review Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. The enhanced P. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage and an altered cell cycle gene regulation within a complex network involving the unfolded protein response, the PI3K/PI3P/AKT pathway, the PfPK4/eIF2α cascade and yet unidentified transcription factor(s), with minimal energetic requirements and fatty acid metabolism maintained in the mitochondrion and apicoplast. The detailed study of these mechanisms offers a way forward for identifying future intervention targets to fend off established artemisinin resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-016-1206-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-09 /pmc/articles/PMC4784301/ /pubmed/26955948 http://dx.doi.org/10.1186/s12936-016-1206-9 Text en © Paloque et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Paloque, Lucie Ramadani, Arba P. Mercereau-Puijalon, Odile Augereau, Jean-Michel Benoit-Vical, Françoise Plasmodium falciparum: multifaceted resistance to artemisinins |
title | Plasmodium falciparum: multifaceted resistance to artemisinins |
title_full | Plasmodium falciparum: multifaceted resistance to artemisinins |
title_fullStr | Plasmodium falciparum: multifaceted resistance to artemisinins |
title_full_unstemmed | Plasmodium falciparum: multifaceted resistance to artemisinins |
title_short | Plasmodium falciparum: multifaceted resistance to artemisinins |
title_sort | plasmodium falciparum: multifaceted resistance to artemisinins |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784301/ https://www.ncbi.nlm.nih.gov/pubmed/26955948 http://dx.doi.org/10.1186/s12936-016-1206-9 |
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