Energy Metabolism of Bloodstream Form Trypanosoma theileri

Abstract

Bloodstream form Trypanosoma theileri degrades glucose to acetate (47%) and succinate (45%) and, therefore, does not solely rely on glycolysis for ATP production. This trypanosomatid does not use amino acids for energy metabolism. These results refute the prevailing hypothesis that substrate availability determines the type of energy metabolism of trypanosomatids.The energy metabolism of Trypanosomatidae varies considerably, not only between species but also between distinct life cycle stages of the same species (7, 17). Several Trypanosomatidae rely on glycolysis of carbohydrates for their ATP production, whereas the energy metabolism of other Trypanosomatidae comprises substantial mitochondrial metabolism in which amino acids are often used as substrates for ATP production. Bloodstream form Trypanosoma brucei, which lives in a glucose-rich environment, is entirely dependent on degradation of glucose into pyruvate by glycolysis, whereas procyclic T. brucei living in the gut of tsetse flies degrades carbohydrates and amino acids by a more-complex metabolism involving substantial mitochondrial metabolism (2, 5, 15). Next to carbohydrate abundance, the type of available nutrients seems to correlate with the differences in energy metabolism in trypanosomatids as well. Insect stages of African trypanosomes and of Trypanosoma cruzi and Leishmania spp. that inhabit arthropod intestines, as well as trypanosomatids that live in intracellular compartments of the endocytotic pathway of mammalian cells, such as amastigote stages of T. cruzi and Leishmania spp., use the abundantly available amino acids in their environment as substrates for energy metabolism involving mitochondrial pathways (4,7,17). Therefore, multiple observations argue for the suggestion that nutrient supply in the natural environment correlates with the energy metabolism present in the distinct trypanosomatid species and life cycle stages.To investigate this possible correlation, we studied the energy metabolism of bloodstream form trypanosomes of the species Trypanosoma theileri, which are extracellular, blooddwelling parasites of mammals, living in a habitat identical to that of bloodstream form T. brucei (3). Although these two bloodstream form trypanosomes inhabit the same environment, these species are not closely related. T. theileri belongs to the subgenus Megatrypanum and, therefore, belongs to the stercorarian section of trypanosomatids, whereas African trypanosomes belong to the section of salivarian trypanosomes (11). T. theileri is a ubiquitous parasite that infects cattle with high incidence all around the world, but these infections are generally considered not to be pathogenic and parasitemia is very low (12,18).Bloodstream form T. theileri isolates were obtained from blood samples derived from Holstein-Frisian cows in The Netherlands. These isolated bloodstream form trypanosomes were expected to be T. theileri, since T. theileri is the only trypanosome species endemic in cows in northwestern Europe (11,18,20). The length of the isolated ...

An Alternative Strategy for Trypanosome Survival in the Mammalian Bloodstream Revealed through Genome and Transcriptome Analysis of the Ubiquitous Bovine Parasite Trypanosoma (Megatrypanum) theileri

“…2 ). This model deduced from differential mRNA levels is consistent with the measured conversion of glucose to succinate in bloodstream form T. theileri ( van Hellemond etal. 2007 ).…”

“… A phylogenetic analysis using sequences of 375 polypeptides universally conserved in trypanosomes confirms earlier work placing T. theileri with the Stercorarian trypanosomes, closer to T. cruzi , T. rangeli , and T. grayi , than to Salivarian trypanosomes such as T. brucei . The core cellular machinery is conserved and comparison of relative transcript abundance with T. brucei identified few major differences, the main exception being in the fate of glycolytic end products with possible secretion of succinate in T. theileri compared with secretion of glycerol in T. brucei , consistent with previous measurements ( van Hellemond etal. 2007 ).…”

“…The core cellular machinery is conserved and comparison of relative transcript abundance with T. brucei identified few major differences, the main exception being in the fate of glycolytic end products with possible secretion of succinate in T. theileri compared with secretion of glycerol in T. brucei , consistent with previous measurements ( van Hellemond etal. 2007 ).…”

Structure of a trypanosomatid mitochondrial cytochrome c with heme attached via only one thioether bond and implications for the substrate recognition requirements of heme lyase

“…Leishmania spp. and T. cruzi) possess a classic mitochondrial respiratory chain [14][15][16]. In others (e.g.…”

Glucose-induced Remodeling of Intermediary and Energy Metabolism in Procyclic Trypanosoma brucei

“…The rate of L-proline consumption in these growth conditions is increased by ϳ6-fold (18). It has been proposed that the procyclic form of T. brucei, as well as other trypanosomatids, adapts its energy metabolism to available carbon sources (4); however, this view has been recently questioned (19,20). Here, we illustrate the metabolic flexibility of procyclic trypanosomes by comparing their L-proline metabolism when grown in glucose-rich and glucose-depleted media.…”