title: 1H-NMR metabolite profiles of different strains of Plasmodium falciparum.
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. 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.
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Rongwei
authors.initials: R
authors.lastname: Teng
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Adele M
authors.initials: AM
authors.lastname: Lehane
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Winterberg
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Shafik
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Summers
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Rowena E
authors.initials: RE
authors.lastname: Martin
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Donelly A
authors.initials: DA
authors.lastname: van Schalkwyk
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Pauline R
authors.initials: PR
authors.lastname: Junankar
authors.affiliation: *Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Kiaran
authors.initials: K
authors.lastname: Kirk
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D053058:Trophozoites / Q000378:metabolism / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine