Authors
P C Steketee2; E Paxton2; F Achcar3; F Giordani3; H de Koning3; T Rowan1; M P Barrett3; L J Morrison2;
1 GALVmed; 2 Roslin Institute; 3 Wellcome Trust Centre for Molecular Parasitology
Discussion
The trypanosome subspecies 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 and as a result, there is a severe
lack of novel therapeutics to counter diseases which affect 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, where 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.