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

Rongwei Teng, Adele M. Lehane, Markus Winterberg, Sarah H. Shafik, Robert L. Summers, Rowena E. Martin, Donelly A. Van Schalkwyk, Pauline R. Junankar, Kiaran Kirk*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)

    Abstract

    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. Chloroquineresistant 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.

    Original languageEnglish
    Pages (from-to)685-699
    Number of pages15
    JournalBioscience Reports
    Volume34
    Issue number6
    DOIs
    Publication statusPublished - 2014

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