1H-NMR metabolite profiles of different strains of Plasmodium falciparum

Although efforts to understand the basis for inter-strain phenotypic variation in the most virulent malaria species, Plasmodium falciparum, have benefited from advances in genomic technologies, there have to date been few metabolomic studies of this parasite. Using 1H-NMR spectroscopy, we have compa...

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Main Authors: Teng, Rongwei, Lehane, Adele M., Winterberg, Markus, Shafik, Sarah H., Summers, Robert L., Martin, Rowena E., van Schalkwyk, Donelly A., Junankar, Pauline R., Kirk, Kiaran
Format: Online
Language:English
Published: Portland Press Ltd. 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240024/
id pubmed-4240024
recordtype oai_dc
spelling pubmed-42400242014-12-01 1H-NMR metabolite profiles of different strains of Plasmodium falciparum Teng, Rongwei Lehane, Adele M. Winterberg, Markus Shafik, Sarah H. Summers, Robert L. Martin, Rowena E. van Schalkwyk, Donelly A. Junankar, Pauline R. Kirk, Kiaran Original Paper Although efforts to understand the basis for inter-strain phenotypic variation in the most virulent malaria species, Plasmodium falciparum, have benefited from advances in genomic technologies, there have to date been few metabolomic studies of this parasite. Using 1H-NMR spectroscopy, we have compared the metabolite profiles of red blood cells infected with different P. falciparum strains. These included both chloroquine-sensitive and chloroquine-resistant strains, as well as transfectant lines engineered to express different isoforms of the chloroquine-resistance-conferring pfcrt (P. falciparum chloroquine resistance transporter). Our analyses revealed strain-specific differences in a range of metabolites. There was marked variation in the levels of the membrane precursors choline and phosphocholine, with some strains having >30-fold higher choline levels and >5-fold higher phosphocholine levels than others. Chloroquine-resistant strains showed elevated levels of a number of amino acids relative to chloroquine-sensitive strains, including an approximately 2-fold increase in aspartate levels. The elevation in amino acid levels was attributable to mutations in pfcrt. Pfcrt-linked differences in amino acid abundance were confirmed using alternate extraction and detection (HPLC) methods. Mutations acquired to withstand chloroquine exposure therefore give rise to significant biochemical alterations in the parasite. Portland Press Ltd. 2014-11-21 /pmc/articles/PMC4240024/ /pubmed/25405893 http://dx.doi.org/10.1042/BSR20140134 Text en © 2014 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Teng, Rongwei
Lehane, Adele M.
Winterberg, Markus
Shafik, Sarah H.
Summers, Robert L.
Martin, Rowena E.
van Schalkwyk, Donelly A.
Junankar, Pauline R.
Kirk, Kiaran
spellingShingle Teng, Rongwei
Lehane, Adele M.
Winterberg, Markus
Shafik, Sarah H.
Summers, Robert L.
Martin, Rowena E.
van Schalkwyk, Donelly A.
Junankar, Pauline R.
Kirk, Kiaran
1H-NMR metabolite profiles of different strains of Plasmodium falciparum
author_facet Teng, Rongwei
Lehane, Adele M.
Winterberg, Markus
Shafik, Sarah H.
Summers, Robert L.
Martin, Rowena E.
van Schalkwyk, Donelly A.
Junankar, Pauline R.
Kirk, Kiaran
author_sort Teng, Rongwei
title 1H-NMR metabolite profiles of different strains of Plasmodium falciparum
title_short 1H-NMR metabolite profiles of different strains of Plasmodium falciparum
title_full 1H-NMR metabolite profiles of different strains of Plasmodium falciparum
title_fullStr 1H-NMR metabolite profiles of different strains of Plasmodium falciparum
title_full_unstemmed 1H-NMR metabolite profiles of different strains of Plasmodium falciparum
title_sort 1h-nmr metabolite profiles of different strains of plasmodium falciparum
description Although efforts to understand the basis for inter-strain phenotypic variation in the most virulent malaria species, Plasmodium falciparum, have benefited from advances in genomic technologies, there have to date been few metabolomic studies of this parasite. Using 1H-NMR spectroscopy, we have compared the metabolite profiles of red blood cells infected with different P. falciparum strains. These included both chloroquine-sensitive and chloroquine-resistant strains, as well as transfectant lines engineered to express different isoforms of the chloroquine-resistance-conferring pfcrt (P. falciparum chloroquine resistance transporter). Our analyses revealed strain-specific differences in a range of metabolites. There was marked variation in the levels of the membrane precursors choline and phosphocholine, with some strains having >30-fold higher choline levels and >5-fold higher phosphocholine levels than others. Chloroquine-resistant strains showed elevated levels of a number of amino acids relative to chloroquine-sensitive strains, including an approximately 2-fold increase in aspartate levels. The elevation in amino acid levels was attributable to mutations in pfcrt. Pfcrt-linked differences in amino acid abundance were confirmed using alternate extraction and detection (HPLC) methods. Mutations acquired to withstand chloroquine exposure therefore give rise to significant biochemical alterations in the parasite.
publisher Portland Press Ltd.
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240024/
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