Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition
Fig 5
Nucleotide metabolism in T. congolense.
Supernatant analysis of T. congolense in vitro cultures showing changes in abundance of D-ribose (A), guanine (B), xanthine (C) and inosine (D) over 56 hours. Grey bar indicates a negative medium control group E) Simplified overview of purine salvage and synthesis in trypanosomatids (adapted from [148]). Numbers indicate the following enzymes: 1, APRT; 2, AD; 3, HGPRT; 4, IMPD; 5, HGXPRT; 6, GMPR; 7, GMPS; 8, HGPRT. Red cross indicates guanine deaminase, which is not encoded/annotated in the T. congolense genome (based on current assembly). F) Comparison of glucose-derived purine carbon labelling in T. congolense and T. brucei [45]. Colours indicate the number of 13C atoms in each metabolite. G) Comparative RNAseq analysis of T. congolense and T. brucei under both in vitro and ex vivo conditions. Gene IDs from top to bottom: PWY0-162 (pyrimidine biosynthesis): PYR1A-B, glutamine hydrolysing carbomoyl phosphate synthase, TbTc_1631; DHODH, dihydroorotate dehydrogenase (fumarate), TbTc_0620; CTPS, cytidine triphosphate synthase, TbTc_0920; PYR3, dihydroorotase, TbTc_3801; PYR2, aspartate carbamoyltransferase, TbTc_1630; CMF40a, nucleoside diphosphate kinase, TbTc_5784; OMPDC/OPRT, orotidine-5-monophosphate decarboxylase/orotate phosphoribosyltransferase, TbTc_0735. PWY0-163 (pyrimidine salvage): CMF40a, nucleoside diphosphate kinase, TbTc_5784; NDPK3, nucleoside diphosphate kinase 3, TbTc_2560; NDPK, nucleoside diphosphate kinase, TbTc_0593; CDA, cytidine deaminase, TbTc_3318; UPRT, uracil phosphoribosyltransferase, TbTc_4220; UP, uridine phosphorylase, TbTc_5794. P121-PWY (adenine/adenosine salvage): ADSL, adenylosuccinate lyase, TbTc_1986; APRT-2, glycosomal adenine phosphoribosyltransferase, TbTc_5918; GMPR, GMP reductase, TbTc_4627; IMPDH1, inosine-5’-monophosphate dehydrogenase, TbTc_1648; HGXPRT, hypoxanthine-guanine-xanthine phosphoribosyltransferase, TbTc_3696; APRT-1, cytosolic adenine phosphoribosyltransferase, TbTc_3522; HGPRT, hypoxanthine-guanine phosphoribosyltransferase, TbTc_0726; ADSS, adenylosuccinate synthetase, TbTc_1142.