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Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy

Glucose is an essential nutrient for Plasmodium falciparum and robust glycolytic activity is indicative of viable parasites. Using NMR spectroscopy, we show that P. falciparum infected erythrocytes consume ~20 times more glucose, and trophozoites metabolize ~6 times more glucose than ring stage para...

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Autores principales: Shivapurkar, Rupali, Hingamire, Tejashri, Kulkarni, Akshay S., Rajamohanan, P. R., Reddy, D. Srinivasa, Shanmugam, Dhanasekaran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305384/
https://www.ncbi.nlm.nih.gov/pubmed/30584241
http://dx.doi.org/10.1038/s41598-018-36197-3
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author Shivapurkar, Rupali
Hingamire, Tejashri
Kulkarni, Akshay S.
Rajamohanan, P. R.
Reddy, D. Srinivasa
Shanmugam, Dhanasekaran
author_facet Shivapurkar, Rupali
Hingamire, Tejashri
Kulkarni, Akshay S.
Rajamohanan, P. R.
Reddy, D. Srinivasa
Shanmugam, Dhanasekaran
author_sort Shivapurkar, Rupali
collection PubMed
description Glucose is an essential nutrient for Plasmodium falciparum and robust glycolytic activity is indicative of viable parasites. Using NMR spectroscopy, we show that P. falciparum infected erythrocytes consume ~20 times more glucose, and trophozoites metabolize ~6 times more glucose than ring stage parasites. The glycolytic activity, and hence parasite viability, can be measured within a period of 2 h to 5 h, using this method. This facilitates antimalarial bioactivity screening on ring and trophozoite stage parasites, exclusively. We demonstrate this using potent and mechanistically distinct antimalarial compounds such as chloroquine, atovaquone, cladosporin, DDD107498 and artemisinin. Our findings indicate that ring stage parasites are inherently more tolerant to antimalarial inhibitors, a feature which may facilitate emergence of drug resistance. Thus, there is a need to discover novel antimalarial compounds, which are potent and fast acting against ring stage parasites. The NMR method reported here can facilitate the identification of such molecules.
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spelling pubmed-63053842018-12-31 Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy Shivapurkar, Rupali Hingamire, Tejashri Kulkarni, Akshay S. Rajamohanan, P. R. Reddy, D. Srinivasa Shanmugam, Dhanasekaran Sci Rep Article Glucose is an essential nutrient for Plasmodium falciparum and robust glycolytic activity is indicative of viable parasites. Using NMR spectroscopy, we show that P. falciparum infected erythrocytes consume ~20 times more glucose, and trophozoites metabolize ~6 times more glucose than ring stage parasites. The glycolytic activity, and hence parasite viability, can be measured within a period of 2 h to 5 h, using this method. This facilitates antimalarial bioactivity screening on ring and trophozoite stage parasites, exclusively. We demonstrate this using potent and mechanistically distinct antimalarial compounds such as chloroquine, atovaquone, cladosporin, DDD107498 and artemisinin. Our findings indicate that ring stage parasites are inherently more tolerant to antimalarial inhibitors, a feature which may facilitate emergence of drug resistance. Thus, there is a need to discover novel antimalarial compounds, which are potent and fast acting against ring stage parasites. The NMR method reported here can facilitate the identification of such molecules. Nature Publishing Group UK 2018-12-24 /pmc/articles/PMC6305384/ /pubmed/30584241 http://dx.doi.org/10.1038/s41598-018-36197-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shivapurkar, Rupali
Hingamire, Tejashri
Kulkarni, Akshay S.
Rajamohanan, P. R.
Reddy, D. Srinivasa
Shanmugam, Dhanasekaran
Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy
title Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy
title_full Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy
title_fullStr Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy
title_full_unstemmed Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy
title_short Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy
title_sort evaluating antimalarial efficacy by tracking glycolysis in plasmodium falciparum using nmr spectroscopy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305384/
https://www.ncbi.nlm.nih.gov/pubmed/30584241
http://dx.doi.org/10.1038/s41598-018-36197-3
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