Discussion

The metabolism of Trypanosoma brucei has several unique features when compared to other eukaryotes. For example, it relies on a partly compartmentalised glycolytic pathway as its only energy supply. Gaining a more detailed knowledge of the parasite's metabolism can help design new drugs and understand the mechanisms of action and resistance of current drugs. LC-MS-based metabolomics using uniformly (U)-₁₃C-labelled glucose enabled Creek et al (PMID: 25775470) to explore T. brucei metabolism more extensively; they found that more pathways use glucose derived carbon than previously thought, including pathways essential to the parasite survival.

This study also raised many new questions. In order to answer them and complete our map of bloodstream form T. brucei metabolism, we used 5 U-₁₃C-labelled amino acids: cysteine, glutamine, methionine, arginine and proline. Parasites were grown in the presence of these labelled amino acids for 48 hours, prior to analysing their intracellular extracts using LC-MS to trace the fate of individual carbon atoms derived from these precursors inside the cells.

The results show the presence of metabolic pathways previously thought to be absent or present only in the insect stage of the parasite. We could also detect the presence of unexpected novel metabolites, likely to be inadvertent products of promiscuous enzymes.