title: Metabolomic analysis of patient plasma yields evidence of plant-like α-linolenic acid metabolism in Plasmodium falciparum.
abstract: Metabolomics offers a powerful means to investigate human malaria parasite biology and host-parasite interactions at the biochemical level, and to discover novel therapeutic targets and biomarkers of infection. Here, we used an approach based on liquid chromatography and mass spectrometry to perform an untargeted metabolomic analysis of metabolite extracts from Plasmodium falciparum-infected and uninfected patient plasma samples, and from an enriched population of in vitro cultured P. falciparum-infected and uninfected erythrocytes. Statistical modeling robustly segregated infected and uninfected samples based on metabolite species with significantly different abundances. Metabolites of the α-linolenic acid (ALA) pathway, known to exist in plants but not known to exist in P. falciparum until now, were enriched in infected plasma and erythrocyte samples. In vitro labeling with (13)C-ALA showed evidence of plant-like ALA pathway intermediates in P. falciparum. Ortholog searches using ALA pathway enzyme sequences from 8 available plant genomes identified several genes in the P. falciparum genome that were predicted to potentially encode the corresponding enzymes in the hitherto unannotated P. falciparum pathway. These data suggest that our approach can be used to discover novel facets of host/malaria parasite biology in a high-throughput manner.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA. viswanathan.lakshmanan@seattlebiomed.org
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Lakshmanan
authors.forename: Kyu Y
authors.initials: KY
authors.lastname: Rhee
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yiting
authors.initials: Y
authors.lastname: Yu
authors.forename: Kamil
authors.initials: K
authors.lastname: Khafizov
authors.forename: Andras
authors.initials: A
authors.lastname: Fiser
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Omar
authors.initials: O
authors.lastname: Ndir
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Daily
mesh_terms: D000293:Adolescent; D000328:Adult; D002853:Chromatography, Liquid; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000378:metabolism / Q000469:parasitology*; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D010944:Plants / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D055815:Young Adult; D017962:alpha-Linolenic Acid / Q000378:metabolism*
chemical_list: D017962:alpha-Linolenic Acid