Trypanosome-binding proteins in the tsetse fly saliva favour the parasite transmission

The tsetse fly salivary gland is the final micro-environment where Trypanosoma brucei parasites adhere and undergo a complex re-programming into an end stage that is again infective for a mammalian host. By the bite of the infected tsetse fly, these trypanosomes are inoculated into the host skin environment together with a complex mixture of salivary gland proteins and metabolites.
This project aims to understand the role of a narrow selection of tsetse saliva proteins in trypanosome development in the fly and transmission to the mammalian host. Based upon our recent experimental data on tsetse protein-trypanosome interactions, the following saliva proteins are selected: (i) a glycine/glutamate-rich protein (Gmmsgp1), (ii) a proline-rich protein (Gmmsgp2) and (iii) a 5'nucleotidase-related protein with a long glutamate/aspartate /asparaginerich domain (Gmmsgp3).
Two complementary experimental approaches will be used to assess the biological role of these saliva proteins in the development and transmission of the T. brucei parasite: (i) specific protein silencing through RNA interference and (ii) constitutive internal delivery of Nanobodies to target the selected saliva proteins. To achieve the latter, we will optimize an innovative paratransgenic approach that makes use of the Sodalis glossinidius endosymbiont to deliver novel Nanobodies against the selected tsetse fly saliva proteins.