Glycerol, a new key player in the trypanosome parasite cycle – TrypaDiff

Trypanosoma (T.) brucei is an extracellular parasite responsible for sleeping sickness in Africa, and is transmitted by a blood-feeding insect vector, the tsetse fly. In its mammalian hosts, the rapidly dividing parasitic forms (slender forms) predominate in the blood and tissues. At the peak of a parasitaemic wave, slender forms differentiate into growth-arrested forms (stumpy forms) in order to protect the host by preventing high parasitaemia. Slender to stumpy differentiation relies on quorum sensing triggered by the accumulation of di- and tripeptides produced by oligopeptidases excreted by the parasites. The current model of T. brucei transmission from mammals to the insect vector emphasises the key role of the quorum sensing-derived stumpy forms produced in the blood. However, this model is still being debated.
Our recent unpublished data showed that glycerol, which is abundant in the skin and adipose tissues where the parasites also reside, induces differentiation of slender into stumpy-like forms, which are transmissible to the vector and competent for differentiation into the parasitic forms present in the insect. We thus propose a rational working hypothesis, in which the glycerol excreted by adipocytes in the skin would induce the production of stumpy-like forms mostly responsible for the parasite transmission to the fly.
To study this new paradigm within our network of 5 complementary partners and collaborators, we will use and develop omics and functional genetics approaches (i) to characterise glycerol-induced stumpy-like forms, (ii) to determine the biological relevance of these parasites, and (iii) to dissect the signalling pathway(s) involved in their glycerol-induced differentiation.
This program will contribute to a better understanding of the developmental biology of trypanosomes responsible for human and domestic animal diseases and it will highlight new ways to control parasite transmission.