Alliance Française contre les Maladies Parasitaires



New research reveals that mammalian stages of trypanosomes can grow in the absence of glucose, if glycerol is provided. The result paves the way for understanding metabolic interactions between extravascular trypanosomes and the glycerol-producing adipocytes present in the skin and adipose tissues. This study was published by Dr Frédéric Bringaud's ParaFrap team and collaborators in November 2018 in the open-access journal PLoS Pathogens.

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Trypanosomes are extracellular parasites that cause devastating neglected tropical diseases affecting humans (sleeping sickness) and domestic animals, such as cattle, horses, camels, pigs, etc. Until very recently, trypanosomes have been considered to propagate exclusively in the glucose-rich mammalian fluids, including the bloodstream. As a result, a dogmatic concept deeply rooted in our scientific community considered that glucose is the only carbon source used by the parasite to fuel its central and energy metabolism.

In the study "Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: analysis of metabolic adaptations on glycerol-rich conditions"the researchers show that replacing glucose by glycerol does not affect long-term growth of the mammalian-infective trypanosomes. The authors described the metabolic adjustments implemented by the parasite to adapt to this unexpected carbon source, including activation of the gluconeogenic pathway, which produces the sugar precursors necessary for essential biosynthetic pathways. These data illustrate the unexpected metabolic flexibility of this parasite highlighted a few years ago by the same research team by revisiting its glucose metabolism.

More importantly, this finding resonates with the recent discovery of extravascular trypanosomes colonizing and proliferating in the immediate vicinity of adipocytes in the skin and the adipose tissues of their mammalian hosts. Glycerol produced in abundance by tissue adipocytes can provide a rational explanation for the development of a glycerol-based metabolism in the mammalian-infective trypanosomes and open new avenues for the development of alternative therapeutic approaches.

bringaud 2018 glycerol