a1 Department of Biochemistry and Molecular Biology, University of Melbourne, 30 Flemington Rd, Parkville, 3010, Victoria, Australia
a2 Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, 30 Flemington Rd, Parkville, 3010, Victoria, Australia
Leishmania spp. are sandfly-transmitted protozoa parasites that cause a spectrum of diseases in humans. Many enzymes involved in Leishmania central carbon metabolism differ from their equivalents in the mammalian host and are potential drug targets. In this review we summarize recent advances in our understanding of Leishmania central carbon metabolism, focusing on pathways of carbon utilization that are required for growth and pathogenesis in the mammalian host. While Leishmania central carbon metabolism shares many features in common with other pathogenic trypanosomatids, significant differences are also apparent. Leishmania parasites are also unusual in constitutively expressing most core metabolic pathways throughout their life cycle, a feature that may allow these parasites to exploit a range of different carbon sources (primarily sugars and amino acids) rapidly in both the insect vector and vertebrate host. Indeed, recent gene deletion studies suggest that mammal-infective stages are dependent on multiple carbon sources in vivo. The application of metabolomic approaches, outlined here, are likely to be important in defining aspects of central carbon metabolism that are essential at different stages of mammalian host infection.
(Received November 11 2009)
(Revised December 23 2009)
(Accepted December 30 2009)
(Online publication February 17 2010)