Glycolysis is important for optimal asexual growth and formation of mature tissue cysts by Toxoplasma gondii
| Autor: | Manuel Llinás, Leah M. Rommereim, Jonathan M. Wastling, Barbara A. Fox, David S. Roos, Anurag Shukla, Dhanasekaran Shanmugam, David J. Bzik, Dong Xia, Kellen L. Olszewski, Daniel P. Beiting |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Glutamine 030106 microbiology Oxidative phosphorylation Pentose phosphate pathway Oxidative Phosphorylation 03 medical and health sciences chemistry.chemical_compound Mice Adenosine Triphosphate Hexokinase Animals Glycolysis Glutaminolysis biology Virulence Gluconeogenesis Toxoplasma gondii Brain Metabolism biology.organism_classification Carbon Metabolic Flux Analysis Cell biology Disease Models Animal 030104 developmental biology Infectious Diseases chemistry Parasitology Phosphoenolpyruvate carboxykinase Toxoplasma Gene Deletion Phosphoenolpyruvate Carboxykinase (ATP) Toxoplasmosis |
| Zdroj: | International journal for parasitology. 48(12) |
| ISSN: | 1879-0135 |
| Popis: | Toxoplasma gondii can grow and replicate using either glucose or glutamine as the major carbon source. Here, we have studied the essentiality of glycolysis in the tachyzoite and bradyzoite stages of T. gondii, using transgenic parasites that lack a functional hexokinase gene (Δhk) in RH (Type-1) and Prugniaud (Type-II) strain parasites. Tachyzoite stage Δhk parasites exhibit a fitness defect similar to that reported previously for the major glucose transporter mutant, and remain virulent in mice. However, although Prugniaud strain Δhk tachyzoites were capable of transforming into bradyzoites in vitro, they were severely compromised in their ability to make mature bradyzoite cysts in the brain tissue of mice. Isotopic labelling studies reveal that glucose-deprived tacyzoites utilise glutamine to replenish glycolytic and pentose phosphate pathway intermediates via gluconeogenesis. Interestingly, while glutamine-deprived intracellular Δhk tachyzoites continued to replicate, extracellular parasites were unable to efficiently invade host cells. Further, studies on mutant tachyzoites lacking a functional phosphoenolpyruvate carboxykinase (Δpepck1) revealed that glutaminolysis is the sole source of gluconeogenic flux in glucose-deprived parasites. In addition, glutaminolysis is essential for sustaining oxidative phosphorylation in Δhk parasites, while wild type (wt) and Δpepck1 parasites can obtain ATP from either glycolysis or oxidative phosphorylation. This study provides insights into the role of nutrient metabolism during asexual propagation and development of T. gondii, and validates the versatile nature of central carbon and energy metabolism in this parasite. |
| Databáze: | OpenAIRE |
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