H2020Индивидуална стипендия2020–2022

Trojan · Redefining Tsetse symbiont bacteria: A Trojan horse against Trypanosome transmission

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-05-01 → 2022-04-30
Финансиране от ЕС: 187 572 €
Участници: 1
Схема: MSCA-IF-EF-CAR

Линиите свързват координатора с партньорите.

Накратко на български

Бактериите в мухата цеце се модифицират, за да разпознават паразити и да произвеждат вещества, които пречат на предаването им. Това е важно, защото съществуващите терапии срещу сънната болест са токсични, трудни за приложение и често неефективни.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Redefining Tsetse symbiont bacteria: A Trojan horse against Trypanosome transmission

African trypanosomiasis is a vector-borne parasitic disease caused by protozoan parasites belonging to the genus Trypanosoma. It is transmitted to humans and animals by tsetse fly bites, causing the sleeping sickness or Human African Trypanosomiasis (HAT) and Nagana or Animal African Trypanosomiasis (AAT). HAT occurs in 36 sub-Saharan African countries in which 70 million inhabitants are at risk, with a prevalence of 300-500 thousand cases. Currently, treatments are unsatisfactory because of the complexity of their administration, the need for hospitalization and their high toxicity. On the other hand, the emergence of multidrug-resistant strains along with the absence of effective vaccines urgently requires the design of new strategies to eradicate the disease. Recently, the existence of a molecular dialogue between the fly, the symbiont Sodalis, and the trypanosome has been demonstrated. Some genes of Sodalis increase or reduce their transcription levels in flies that had been infected by the parasites, even if the parasite is not established in the fly's midgut. This opens the door to the identification of promoters of Sodalis that can be induced by Trypanosoma to design Sodalis strains expressing certain compounds that hinder the vector competence (VC) only when it is infected. Based on the above, the main objective of this project was the 1) the design of a new expression system in Sodalis sp. induced by the parasite, so that it was only active in infected flies, reducing or eliminating its ability to transfer the parasite through different routes and 2) the identification and evaluation of new compounds able to kill the parasite.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

RIJKSUNIVERSITEIT GRONINGEN · GroningenКоординаторНидерландия