Authors

Discussion

myo-Inositol is one of the nine naturally occurring inositol stereoisomers. It is ubiquitous amongst eukaryotes and acts as an essential metabolite with roles in signal transduction and membrane formation. In the protozoan parasite Trypanosoma cruzi—the causative agent of Chagas’ disease—myo-inositol acts as a precursor to phosphatidylinositol (PI), an essential membrane lipid component. PI in turn is then required for formation of inositol phosphoceramide (IPC), various phosphoinositides, and glycophosphatidylinositol (GPI)-anchored mucin-type glycoproteins, which coats the parasite’s cell-surface allowing the parasite to participate in multiple essential steps in parasite-host interactions.

In T. cruzi, myo-inositol is proposed to be both de novo synthesised and scavenged from the environment, however, the proteins involved in both pathways have not been fully studied in T. cruzi. Therefore, the aim of this project is to genetically validate and biochemically characterise the putative inositol-3-phosphate synthase (TcINO1) from the de novo synthesis pathway as well as the myo-inositol transporter (TcMIT) from the extracellular uptake pathway.

Both proteins—TcINO1 and TcMIT—are genetically validated as essential and biochemically characterised. In addition, localisation and phenotyping of TcINO1 and TcMIT genetically altered T. cruzi has been completed, which helps establishes how T. cruzi differentiate between de novo and scavenged myo-inositol.