Metabolic signatures of Besnoitia besnoiti -infected endothelial host cells and blockage of key metabolic pathways indicate high glycolytic and glutaminolytic needs of the parasite

摘要: Besnoitia besnoiti is an obligate intracellular and emerging coccidian parasite of cattle with a significant economic impact on industry. During acute infection, fast-proliferating tachyzoites are continuously formed mainly in endothelial host cells infected animals. Given that offspring formation highly energy cell building block demanding process, the needs to exploit cellular metabolism meet its metabolic demands. Here, we analyzed signatures B. besnoiti-infected aimed influence proliferation by inhibitors specific pathways. The following were tested: fluoro 2-deoxy-D-glucose (FDG, DG; glycolysis), 6-diazo-5-oxo-L-norleucin (DON; inhibitor glutaminolysis), dichloroacetate (DCA; pyruvate dehydrogenase kinase which favorites channeling glucose carbons into TCA cycle) adenosine-monophosphate (AMP; ribose 5-P synthesis). Overall, infections bovine induced infection rate-dependent increase glucose, lactate, glutamine, glutamate, pyruvate, alanine, serine conversion rates together indicate parasite-triggered up-regulation glycolysis glutaminolysis. Thus, addition DON, FDG, DG cultivation medium led dose-dependent inhibition replication (4 μM 99.5 % inhibition; 2 mM 99.1 % DG, 93 % 8 mM DCA, 71.9 % inhibition). In contrast, AMP had no effects total tachyzoite production up concentration 20 mM. Together, these data may open new strategies for development therapeutics infections.