A Toxoplasma gondii Gluconeogenic Enzyme Contributes to Robust Central Carbon Metabolism and Is Essential for Replication and Virulence
Martin Blume, Richard Nitzsche, Ulrich Sternberg, Motti Gerlic, Seth L Masters, Nishith Gupta, Malcolm J McConville
Cell Host & Microbe | CELL PRESS | Published : 2015
The expression of gluconeogenic enzymes is typically repressed when glucose is available. The protozoan parasite Toxoplasma gondii utilizes host glucose to sustain high rates of intracellular replication. However, despite their preferential utilization of glucose, intracellular parasites constitutively express two isoforms of the gluconeogenic enzyme fructose 1,6-bisphosphatase (TgFBP1 and TgFBP2). The rationale for constitutive expression of FBPases in T. gondii remains unclear. We find that conditional knockdown of TgFBP2 results in complete loss of intracellular growth in vitro under glucose-replete conditions and loss of acute virulence in mice. TgFBP2 deficiency was rescued by expressio..View full abstract
Awarded by Australian NHMRC
Awarded by German Research Foundation (DFG)
Awarded by DFG
We thank Chris Tonkin, Giel van Dooren, Boris Striepen, Dominque Soldati-Favre, Paul Gleeson, and Geoff McFadden for generously sharing antibodies, plasmids, and parasite lines. We also thank Julie Ralton for experimental advice and Stuart Ralph for critical reading of the manuscript. This work was supported by Australian NHMRC project grant APP1057815. M.J.M. is a NHMRC Principal Research fellow. M.B. was supported by a DFG research fellowship and a PhD fellowship from the Helmholtz Foundation of Germany (Humboldt University of Berlin). N.G. was supported by German Research Foundation (DFG) grants GRK1121/A7 and a DFG grant GU1100/3-1.