Carbon metabolism and metabolic control of the acute and chronic stages in Toxoplasma gondii

• Applicant: Dr. Nishith Gupta
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 242288771

Toxoplasma gondii is an obligate intracellular parasite of nearly all warm-blooded vertebrates, and serves as a model pathogen to understand the biology of other related parasites. Successful infection and transmission of T. gondii depends on its ability to switch between the fast replicating tachyzoite (acute) and quiescent bradyzoite (chronic) stages. Inter-conversion of the two stages coincides with an adjustment of the biomass and parasite metabolism. A stringent mutual regulation of carbon pathways (glycolysis, TCA cycle, pentose phosphate pathway, gluconeogenesis) is central to accommodate the variable metabolic needs of the two stages. We have revealed glucose and glutamine as the two major nutrients, satisfying the bioenergetic requirements of tachyzoites. We now aim to study the metabolic cooperativity of both nutrients in tachyzoites and bradyzoites, and how metabolism controls epigenetic acetylation and stage switching in T. gondii. To advance this work, we have designed an optogenetic parasite strain that allows an efficient bradyzoite conversion upon a brief photo-induction of cytosolic cAMP. Other established methods to this end include making and phenotyping of the parasite mutants, stable and radioisotope labelling, subcellular localization and enzyme activity assays, all of which will be implemented to determine the biological importance, spatial flow and kinetic control of the carbon flux in the parasite. This work should reveal how the carbon metabolism is rewired upon acute/chronic stage switches, as well as metabolic control of epigenetics, and nutritional adaptations in T. gondii.

• DFG Programme: Research Grants