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  • The EMBO Journal (2007) 26, 1094 - 1104
  • doi:10.1038/sj.emboj.7601565

Published online: 8 February 2007

Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania

Kai Zhang1,a, Justine M Pompey1, Fong-Fu Hsu2, Phillip Key1, Padmavathi Bandhuvula3, Julie D Saba3, John Turk2 and Stephen M Beverley1

  1. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA
  2. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
  3. Children's Hospital Oakland Research Institute, Center for Cancer Research, Oakland, CA, USA

Correspondence to:

Stephen M Beverley, Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., Box 8230, St Louis, MO 63110, USA. Tel.: +1 314 747 2630; Fax: +1 314 747 2634; E-mail: beverley@borcim.wustl.edu

aPresent address: Department of Biological Sciences, Texas Tech University, Box 43131, Lubbock, TX 79409, USA

Received 11 July 2006; Accepted 20 December 2006

In most eukaryotes, sphingolipids (SLs) are critical membrane components and signaling molecules. However, mutants of the trypanosomatid protozoan Leishmania lacking serine palmitoyltransferase (spt2-) and SLs grow well, although they are defective in stationary phase differentiation and virulence. Similar phenotypes were observed in sphingolipid (SL) mutant lacking the degradatory enzyme sphingosine 1-phosphate lyase (spl-). This epistatic interaction suggested that a metabolite downstream of SLs was responsible. Here we show that unlike other organisms, the Leishmania SL pathway has evolved to be the major route for ethanolamine (EtN) synthesis, as EtN supplementation completely reversed the viability and differentiation defects of both mutants. Thus Leishmania has undergone two major metabolic shifts: first in de-emphasizing the metabolic roles of SLs themselves in growth, signaling, and maintenance of membrane microdomains, which may arise from the unique combination of abundant parasite lipids; Second, freed of typical SL functional constraints and a lack of alternative routes to produce EtN, Leishmania redirected SL metabolism toward bulk EtN synthesis. Our results thus reveal a striking example of remodeling of the SL metabolic pathway in Leishmania.

  • Keywords:

    • metacyclogenesis,
    • phosphatidylethanolamine,
    • sphingolipid,
    • sphingosine-1-phosphate lyase,
    • virulence