TY - JOUR
T1 - Metabolomic analysis of patient plasma yields evidence of plant-like-linolenic acid metabolism in plasmodium falciparum
AU - Lakshmanan, Viswanathan
AU - Rhee, Kyu Y.
AU - Wang, Wei
AU - Yu, Yiting
AU - Khafizov, Kamil
AU - Fiser, Andras
AU - Wu, Peng
AU - Ndir, Omar
AU - Mboup, Souleymane
AU - Ndiaye, Daouda
AU - Daily, Johanna P.
N1 - Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (Grant No. R01AI077623). Potential conflicts of interest. All authors: No reported conflicts.
PY - 2012/7/15
Y1 - 2012/7/15
N2 - 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-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.
AB - 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-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.
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U2 - 10.1093/infdis/jis339
DO - 10.1093/infdis/jis339
M3 - Article
C2 - 22566569
AN - SCOPUS:84862867275
SN - 0022-1899
VL - 206
SP - 238
EP - 248
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -