Journal article

Role of hexosamine biosynthesis in Leishmania growth and virulence

Thomas Naderer, Edmund Wee, Malcolm J McConville



Leishmania parasites incorporate N-acetylglucosamine (GlcNAc) into surface-expressed glycosylphosphatidylinositol (GPI) glycolipids and N-linked glycans. To investigate whether these glycoconjugates are required for infectivity of promastigote and intracellular amastigote stages, we generated a Leishmania major mutant lacking the gene encoding glutamine : fructose-6-phosphate amidotransferase (GFAT). The L. majorDeltagfat mutant is unable to synthesize GlcN-6-phosphate de novo and is auxotrophic for GlcN or GlcNAc. GlcN starvation leads to the rapid depletion of dolichol-linked oligosaccharides and GPI precursors, hypersensitivity to elevated temperatures encountered in the mammalian host an..

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Funding Acknowledgements

We thank Prof. Steve Beverley (Washington University, USA) for providing the pXG plasmids, Dr Emanuela Handman (the Walter and Eliza Hall Institute of Medical Research, Melbourne) and Thomas Ilg (Intervet Innovation GmBH, Germany) for anti-gp63 and LT15 antibodies and G. Koeglreiter for IT support. This work was funded by the Australian National Health and Medical Research Council. M.J.M. is a NHMRC Principal Research Fellow. The authors declare no financial conflicts.