Authors

Discussion

Pathogenic animal trypanosomes infecting livestock have a significant economic and social impact in endemic areas. Trypanosoma congolense, which is particularly pathogenic in cattle, is currently controlled with chemotherapy and chemoprophylaxis, however, existing compounds are losing efficacy due to the emergence of drug-resistant parasites. Therefore, probing metabolic pathways will assist the development of in vitro culture methods, vital to the discovery of novel trypanocidal compounds. Our current understanding of the mitochondrial metabolism of trypanosomatids is mostly derived from studies involving T. brucei. However, our preliminary data show that the central carbohydrate metabolism of T. brucei differs to that of other, lesser studied livestock trypanosome species such as T. congolense and T. vivax. For example, T. congolense was shown to consume glucose at lower rates in vitro than T. brucei, and untargeted metabolomic analyses showed that less pyruvate is excreted as a metabolic end-product. Here, we investigate the source of mitochondrial acetate production in bloodstream form T. congolense IL3000 and T. brucei 427. Acetate was found to be excreted by T. congolense at significantly higher rates than T. brucei (138.0 vs. 16.6 nM/min/10⁸ cells). ¹H-NMR spectrometry revealed the primary sources of acetate production in T. congolense to be glucose-derived pyruvate and L-threonine. In vitro drug inhibition assays showed T. congolense to be more sensitive than T. brucei to inhibition with the pyruvate transport inhibitor UK5099, and the pyruvate dehydrogenase inhibitor arsenite (59.9 nM vs. 134.6 nM; 139.9 μM vs. 292.0 μM), suggesting an increased dependence on the mitochondrial acetate pathway in T. congolense. Together, these data suggest that bloodstream form T. congolense display similar metabolic characteristics to procyclic (insect-stage) T. brucei. This strengthens the previous observation that mitochondrial metabolism is distinctly different between T. congolense and T. brucei.