Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.

<h4>Background</h4>Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, c...

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Autores principales:	Maria Isabel Veiga, Pedro Eduardo Ferreira, Berit Aydin Schmidt, Ulf Ribacke, Anders Björkman, Ales Tichopad, José Pedro Gil
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe4c90a6830044bca342d1c463a956b6
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spelling	oai:doaj.org-article:fe4c90a6830044bca342d1c463a956b62021-11-18T06:35:43ZAntimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.1932-620310.1371/journal.pone.0012408https://doaj.org/article/fe4c90a6830044bca342d1c463a956b62010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20811640/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum.<h4>Methodology/principal findings</h4>We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the expression of four genes coding for confirmed and putative drug transporters (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described dose and clone dependent delay in the intra-erythrocytic cycle of the parasite. Drug impact on cell cycle progression and gene expression was then merged using a non-linear regression model to determine specific drug driven expression. This revealed a mild, but significant, mefloquine driven gene induction up to 1.5 fold.<h4>Conclusions/significance</h4>Both cell cycle delay and induced gene expression represent potentially important mechanisms for parasites to escape the effect of the antimalarial drug.Maria Isabel VeigaPedro Eduardo FerreiraBerit Aydin SchmidtUlf RibackeAnders BjörkmanAles TichopadJosé Pedro GilPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12408 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Isabel Veiga Pedro Eduardo Ferreira Berit Aydin Schmidt Ulf Ribacke Anders Björkman Ales Tichopad José Pedro Gil Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
description	<h4>Background</h4>Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum.<h4>Methodology/principal findings</h4>We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the expression of four genes coding for confirmed and putative drug transporters (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described dose and clone dependent delay in the intra-erythrocytic cycle of the parasite. Drug impact on cell cycle progression and gene expression was then merged using a non-linear regression model to determine specific drug driven expression. This revealed a mild, but significant, mefloquine driven gene induction up to 1.5 fold.<h4>Conclusions/significance</h4>Both cell cycle delay and induced gene expression represent potentially important mechanisms for parasites to escape the effect of the antimalarial drug.
format	article
author	Maria Isabel Veiga Pedro Eduardo Ferreira Berit Aydin Schmidt Ulf Ribacke Anders Björkman Ales Tichopad José Pedro Gil
author_facet	Maria Isabel Veiga Pedro Eduardo Ferreira Berit Aydin Schmidt Ulf Ribacke Anders Björkman Ales Tichopad José Pedro Gil
author_sort	Maria Isabel Veiga
title	Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
title_short	Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
title_full	Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
title_fullStr	Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
title_full_unstemmed	Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
title_sort	antimalarial exposure delays plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/fe4c90a6830044bca342d1c463a956b6
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Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.

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