Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax

Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium v...

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Autores principales: Imwong, Mallika, Russell, Bruce, Suwanarusk, Rossarin, Nzila, Alexis, Leimanis, Mara L., Sriprawat, Kanlaya, Kaewpongsri, Supaporn, Phyo, Aung Pyae, Snounou, Georges, Nosten, Francois, Renia, Laurent
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Major Articles and Brief Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071051/
https://www.ncbi.nlm.nih.gov/pubmed/21288820
http://dx.doi.org/10.1093/infdis/jiq024
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author Imwong, Mallika
Russell, Bruce
Suwanarusk, Rossarin
Nzila, Alexis
Leimanis, Mara L.
Sriprawat, Kanlaya
Kaewpongsri, Supaporn
Phyo, Aung Pyae
Snounou, Georges
Nosten, Francois
Renia, Laurent
author_facet Imwong, Mallika
Russell, Bruce
Suwanarusk, Rossarin
Nzila, Alexis
Leimanis, Mara L.
Sriprawat, Kanlaya
Kaewpongsri, Supaporn
Phyo, Aung Pyae
Snounou, Georges
Nosten, Francois
Renia, Laurent
author_sort Imwong, Mallika
collection PubMed
description Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC(50)](,) 13,345 nM), these parasites were all highly susceptible to MTX (median IC(50,) 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation.
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spelling pubmed-30710512012-01-15 Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax Imwong, Mallika Russell, Bruce Suwanarusk, Rossarin Nzila, Alexis Leimanis, Mara L. Sriprawat, Kanlaya Kaewpongsri, Supaporn Phyo, Aung Pyae Snounou, Georges Nosten, Francois Renia, Laurent J Infect Dis Major Articles and Brief Reports Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC(50)](,) 13,345 nM), these parasites were all highly susceptible to MTX (median IC(50,) 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation. Oxford University Press 2011-01-15 /pmc/articles/PMC3071051/ /pubmed/21288820 http://dx.doi.org/10.1093/infdis/jiq024 Text en © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Brief Reports
Imwong, Mallika
Russell, Bruce
Suwanarusk, Rossarin
Nzila, Alexis
Leimanis, Mara L.
Sriprawat, Kanlaya
Kaewpongsri, Supaporn
Phyo, Aung Pyae
Snounou, Georges
Nosten, Francois
Renia, Laurent
Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax
title Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax
title_full Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax
title_fullStr Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax
title_full_unstemmed Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax
title_short Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax
title_sort methotrexate is highly potent against pyrimethamine-resistant plasmodium vivax
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071051/
https://www.ncbi.nlm.nih.gov/pubmed/21288820
http://dx.doi.org/10.1093/infdis/jiq024
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