Authors

P C Steketee²; F Achcar³; F Giordani³; E Paxton²; S Jayaraman²; A Donachie³; M Witty¹; R Peter¹; H de Koning³; M P Barrett³; L J Morrison²;  ¹ GALVmed;  ² Roslin Institute;  ³ Wellcome Trust Centre for Molecular Parasitology

Discussion

The trypanosome species Trypanosoma congolense and T. vivax are the primary causative agents of animal African trypanosomiasis (AAT). In contrast to T. brucei, our biological knowledge of these parasites remains limited. As a result, there is a severe lack of novel therapeutics to counter AAT, which affects tens of millions of livestock annually. Moreover, there have been no new drugs for >50 years and resistance has been reported to the few veterinary trypanocides available. One of the key issues in studying AAT remains our limited ability to culture both T. congolense and T. vivax. The primary aim of this project is the use of omics-driven approaches to further our understanding of both T. congolense and T. vivax, with a view to developing optimised in vitro culturing media that will enable the culture of field isolates, as well as high-throughput in vitro drug screens. Using a metabolomics-driven approach, we have identified key differences in the metabolic usage and output of bloodstream forms of a laboratory-adapted T. congolense strain (IL3000). We have shown that the parasite consumes significantly less glucose than T. brucei and excretes large amounts of succinate and malate, in contrast to T. brucei, for which pyruvate is a primary output. These data suggest bloodstream form T. congolense is not solely reliant upon glycolysis, but also utilises other metabolic pathways for central carbon metabolism, highlighting significant metabolic differences between T. congolense and T. brucei that could have important implications in therapeutic design.