Host-Parasite Interactions Revealed by Plasmodium falciparum Metabolomics

Kellen L. Olszewski, Joanne M. Morrisey, Daniel Wilinski, James M. Burns, Akhil B. Vaidya, Joshua D. Rabinowitz, Manuel Llinás

Research output: Contribution to journalArticle

185 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalCell Host and Microbe
Volume5
Issue number2
DOIs
StatePublished - Feb 19 2009

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Keywords

  • CHEMBIO
  • MICROBIO
  • SYSBIO

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    Olszewski, K. L., Morrisey, J. M., Wilinski, D., Burns, J. M., Vaidya, A. B., Rabinowitz, J. D., & Llinás, M. (2009). Host-Parasite Interactions Revealed by Plasmodium falciparum Metabolomics. Cell Host and Microbe, 5(2), 191-199. https://doi.org/10.1016/j.chom.2009.01.004