Redefining Tsetse symbiont bacteria: A Trojan horse against Trypanosome transmission

Descripción del proyecto

Actuación sobre la bacteria simbionte de la glosina para luchar contra la transmisión de «Trypanosoma»

La tripanosomiasis africana causada por «Trypanosoma brucei» es una de las principales causas de pobreza en el continente africano. Aparte de infectar a humanos, también afecta al desarrollo de la ganadería de animales domesticados al provocar la tripanosomosis africana o nagana cuando ataca al ganado. El proyecto financiado con fondos europeos Trojan propone un desarrollo conceptual del método terapéutico contra la tripanosomosis africana que se dirige contra el vector del parásito, la glosina, para luchar así tanto contra la tripanosomosis africana en humanos como en animales. El método aprovecha los avances de la biología molecular moderna al diseñar un nuevo sistema de expresión para reducir o eliminar la capacidad del vector para utilizar uno de los endosimbiontes de la glosina, la bacteria «Sodalis». La interrupción de la transmisión del parásito contribuirá a una reducción drástica de los efectos de la tripanosomosis en el continente africano.

Objetivo

African trypanosomiasis has been a historic scourge on the African continent and one of the major causes of poverty. It is responsible for sleeping sickness in humans and it avoids the development of agriculture based on domesticated animals where it causes Nagana. It is a neglected disease with the worst drug control according to WHO. In this project, I propose a conceptual change in the therapeutic approach against Trypanosoma sp., being the goal of the proposal to eliminate the parasite in its vector, the tsetse fly, thus fighting both, sleeping sickness and Nagana. Taking advantage of the current methodological advances, the claim of this innovative proposal is the design of a new expression system to reduce or eliminate the vector competence, using for it one of the endosymbionts of the fly, Sodalis sp. The development of this idea involves a work of entomology, microbiology, parasitology and molecular biology. For this study, 2 research groups with solid and complementary expertise and skills are required: The French National Research Institute for Sustainable Development (France) and the University of Groningen (The Netherlands). The methodology implemented in this project will be: (i) characterization of proteins secretion pathways in Sodalis for heterologous expression of peptides, (ii) identification of promoters overexpressed in Sodalis upon interaction with Trypanosoma, and their characterization by fusion to fluorescent proteins, iii) paratransgenesis assays in flies and evaluation of the in vivo activity in infected and non-infected flies, stability across time and inherency to progeny, iv) analysis of the vector competence, using the new expression system by the production of antimicrobial peptides active against Trypanosoma, production of insecticidal peptides to kill the flies infected and RNA interference with the fly/symbionts. Blocking parasite transmission, we will contribute to drastically reduce the impact of trypanosome on African health.