Metabolomic Characterisation of Host-Parasite-Interactions of the Apicomplexans Toxoplasma gondii and Plasmodium falciparum

• Applicant: Dr. Martin Blume
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 223103804

Toxoplasma gondii and Plasmodium falciparum are important human pathogens. As obligate intracellular parasites they depend entirely on the uptake of host nutrients. However, it remains unclear how the nutrient availability influences their physiology. T. gondii infects virtually any warm-blooded animal and has a very flexible energy metabolism. In the absence of exogenous glucose it can utilise other carbon sources to satisfy its need for hexoses via gluconeogenesis. However, the availability and significance of non-hexose nutrients for intracellular T. gondii is largely uncharacterised. In contrast, intraerythrocytic Plasmodium parasites absolutely depend on glucose uptake but recent transcriptomic studies on clinical isolates suggested a conditional co-utilisation of other carbon sources. However, a lack of culture systems that provide natural nutrient environments conceals the functional capabilities of the Plasmodiums metabolism. To address these fundamental questions we propose the following research:1 Identification of carbon sources for T. gondii by metabolite profiling of infected host cells2 Testing of the significance of gluconeogenesis in T. gondii3 Establishment of chemostat P. falciparum cultures to define physiological states via metabolic footprinting and isotopomer labelling4 Identification of individual roles of glucose and their redundancy with alternative nutrients in P. falciparumWe will characterise metabolic host-parasite interactions by investigating the metabolic structure and dynamics of two complementary apicomplexan parasites in context of defined nutrient environments. To this end we will use an established gas and liquid chromatography-mass spectrometry and NMR-based analytical platform. Understanding the plasticity of parasite metabolism in physiological scenarios is urgently required to reveal critical host-parasite interactions and to evaluate the in vivo mode of action and resistance mechanisms of parasitocidal drugs.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Hosts: Professor Dr. Malcolm McConville; Dr. Stuart Alexander Ralph