1H-NMR metabolite profiles of different strains of Plasmodium falciparum
| Autor: | Sarah H. Shafik, Kiaran Kirk, Robert L. Summers, Markus Winterberg, Adele M. Lehane, Rowena E. Martin, Rongwei Teng, Pauline R. Junankar, Donelly A. van Schalkwyk |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Erythrocytes
Metabolite Proton Magnetic Resonance Spectroscopy lcsh:Life lcsh:QR1-502 CQ chloroquine Drug Resistance Protozoan Proteins uRBC uninfected red blood cell Biochemistry lcsh:Microbiology chemistry.chemical_compound Xenopus laevis 0302 clinical medicine Chloroquine Choline cRBC co-cultured red blood cell iRBC infected red blood cell Chromatography High Pressure Liquid Phosphocholine chemistry.chemical_classification 0303 health sciences biology chloroquine resistance 1H-NMR RBC red blood cell GABA 4-aminobutyrate 3. Good health Amino acid Metabolome Female medicine.drug PfCRT CQR CQ-resistant Plasmodium falciparum Biophysics malaria TCA tricarboxylic acid Virulence CQS CQ-sensitive Host-Parasite Interactions 03 medical and health sciences Antimalarials Species Specificity parasitic diseases medicine Animals Humans Metabolomics Trophozoites Molecular Biology 030304 developmental biology Original Paper TSP trimethylsilyl-2 2 3 3-tetradeuteropropionic acid DV digestive vacuole PfCRT Plasmodium falciparum chloroquine resistance transporter Membrane Transport Proteins Cell Biology biology.organism_classification lcsh:QH501-531 chemistry Mutation Oocytes HPLC 030217 neurology & neurosurgery |
| Zdroj: | Bioscience Reports Bioscience Reports, Vol 34, Iss 6, p e00150 (2014) |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | 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. The metabolite profiles of red blood cells infected with different malaria parasite strains were compared. Amino acid profiles varied with the chloroquine resistance status of the strain, and this was linked specifically to mutations in the parasite's chloroquine resistance transporter. |
| Databáze: | OpenAIRE |
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