Plasmodium falciparum is dependent on de novo myo-inositol biosynthesis for assembly of GPI glycolipids and infectivity

JI Macrae; S Lopaticki; AG Maier; T Rupasinghe; A Nahid; AF Cowman; MJ Mcconville

Journal article

Plasmodium falciparum is dependent on de novo myo-inositol biosynthesis for assembly of GPI glycolipids and infectivity

JI Macrae, S Lopaticki, AG Maier, T Rupasinghe, A Nahid, AF Cowman, MJ Mcconville

Molecular Microbiology | WILEY | Published : 2014

DOI: 10.1111/mmi.12496

Download PDF

Abstract

Intra-erythrocytic stages of the malaria parasite, Plasmodium falciparum, are thought to be dependent on de novo synthesis of phosphatidylinositol, as red blood cells (RBC) lack the capacity to synthesize this phospholipid. The myo-inositol headgroup of PI can either be synthesized de novo or scavenged from the RBC. An untargeted metabolite profiling of P.falciparum infected RBC showed that trophozoite and schizont stages accumulate high levels of myo-inositol-3-phosphate, indicating increased de novo biosynthesis of myo-inositol from glucose 6-phosphate. Metabolic labelling studies with 13C-U-glucose in the presence and absence of exogenous inositol confirmed that de novo myo-inositol synth..

View full abstract

University of Melbourne Researchers

Sash Lopaticki Author

Malcolm McConville Author

Related Projects (1)

Metabolomic analysis of malaria and antimalarial drugs

There is an urgent need to develop new drugs to treat malaria, one of the most important diseases to afflict humanity. We have developed new..

Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Funding Acknowledgements

We thank Ms Monica Brown at the Walter and Eliza Hall Institute of Medical Research for technical assistance, Professor Andrew Holmes for providing authentic myo-inositol 3-phosphate, Dr Maria Doyle (Melbourne University) for discussions, and the Australian Red Cross Blood service (Melbourne), for provision of serum. This work was supported by program (APP406601) and project (APP1006024) grants and the Independent Research Institute Infrastructure Support Scheme from the National Health and Medical Research Council of Australia (NHMRC) and the Victorian State Government Operational Infrastructure Support Scheme. J.I.M. was supported by a Royal Society Travelling Fellowship. M.J.M. is an NHMRC Principal Research Fellow. A.F.C. is an International Scholar of the Howard Hughes Medical Institute. A.G.M. is an ARC Australian Research Fellow. None of the authors have a conflict of interest with the work reported in this study.