title: Host-parasite interactions revealed by Plasmodium falciparum metabolomics.
abstract: Intracellular pathogens have devised mechanisms to exploit their host cells to ensure their survival and replication. The malaria parasite Plasmodium falciparum relies on an exchange of metabolites with the host for proliferation. Here we describe a mass spectrometry-based metabolomic analysis of the parasite throughout its 48 hr intraerythrocytic developmental cycle. Our results reveal a general modulation of metabolite levels by the parasite, with numerous metabolites varying in phase with the developmental cycle. Others differed from uninfected cells irrespective of the developmental stage. Among these was extracellular arginine, which was specifically converted to ornithine by the parasite. To identify the biochemical basis for this effect, we disrupted the plasmodium arginase gene in the rodent malaria model P. berghei. These parasites were viable but did not convert arginine to ornithine. Our results suggest that systemic arginine depletion by the parasite may be a factor in human malarial hypoargininemia associated with cerebral malaria pathogenesis.
authors.affiliation: Department of Molecular Biology, 2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Kellen L
authors.initials: KL
authors.lastname: Olszewski
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Morrisey
authors.forename: Daniel
authors.initials: D
authors.lastname: Wilinski
authors.forename: James M
authors.initials: JM
authors.lastname: Burns
authors.forename: Akhil B
authors.initials: AB
authors.lastname: Vaidya
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: Manuel
authors.initials: M
authors.lastname: Llinás
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions; D006801:Humans; D008288:Malaria / Q000469:parasitology; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D051379:Mice; D009952:Ornithine / Q000378:metabolism; D010962:Plasmodium berghei / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D001120:Arginine; D009952:Ornithine; D001119:Arginase