Journal Article

Metabolomic Analysis of Patient Plasma Yields Evidence of Plant-Like α-Linolenic Acid Metabolism in <i>Plasmodium falciparum</i>

Viswanathan Lakshmanan, Kyu Y. Rhee, Wei Wang, Yiting Yu, Kamil Khafizov, Andras Fiser, Peng Wu, Omar Ndir, Souleymane Mboup, Daouda Ndiaye and Johanna P. Daily

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 206, issue 2, pages 238-248
Published in print July 2012 | ISSN: 0022-1899
Published online May 2012 | e-ISSN: 1537-6613 | DOI: http://dx.doi.org/10.1093/infdis/jis339
Metabolomic Analysis of Patient Plasma Yields Evidence of Plant-Like α-Linolenic Acid Metabolism in Plasmodium falciparum

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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 13C-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.

Journal Article.  5752 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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