HEИндивидуална стипендия2022–2024

SF-Leishyb · Impact of Reactive Oxygen Species produced by their sand fly vector on Leishmania sexual hybrid formation

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

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 211 755 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Паразитите Leishmania се изследват, за да се разбере дали активните кислородни форми в червата на пясъчните мухи стимулират тяхното сексуално размножаване и създаване на хибриди. Това помага да се обясни генетичното разнообразие на паразитите, което влияе върху тежестта на болестта и устойчивостта към лекарства.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Impact of Reactive Oxygen Species produced by their sand fly vector on Leishmania sexual hybrid formation

Leishmania parasites are the causative agents of leishmaniasis, a disease characterized by a wide spectrum of symptoms ranging from cutaneous lesions to fatal visceral damages. This large diversity of clinical outcomes is due to the high genetic diversity of the parasite strains. Leishmania typically reproduce by clonal division but on rare occasions they can also undergo a cryptic sexual cycle, resulting in the production of hybrid progeny. This sexual mating is believed to be a significant source of genetic diversity in Leishmania, and can lead to changes in tissue tropism, pathology, or even drug resistance. Leishmania hybrids can be generated experimentally, in vivo by co-infecting Phlebotomine sand flies (the vector insects harboring Leishmania) or in in vitro axenic cultures. However, the frequency of hybrids generated in vivo is notably much higher than in vitro, despite the ability to culture large quantities of parasites, indicating that the gut environment is particularly conducive to Leishmania sexual mating. The exact mechanisms of Leishmania sexual reproduction and the factors that make the vector’s gut favorable for this process remain unknown and are the focus of this project. I previously showed that exposing parental parasite cultures to Reactive Oxygen Species (ROS) increases hybrid production in vitro, which led me to hypothesize that ROS, present in the sand fly gut, could be a key factor in promoting Leishmania sexual reproduction. The project SF-Leishyb aimed to explore the mechanisms of Leishmania hybrid production and the investigate the impact of ROS present in the sand fly gut on the engagement of the parasites in a sexual reproduction path. The project presented two objectives: 1) to decipher the impact of the ROS present in the sand fly gut on Leishmania sexual reproduction in vivo by modify the ROS gut levels through food supplementation and/or sand fly genome editing; and 2) to uncover the role of Leishmania candidate genes including oxidant detoxification enzymes and DNA repair factors on parasite sexual reproduction through parasite genome editing and experimental hybrid production.

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

Цел на проекта

By transmitting hundreds of pathogens causing important human mortality and morbidity, vector insects are a major public health threat. Even if intrinsic insect parameters such as immune response are known to impact their vectorial capacities, the vector/pathogen interaction is still little understood. Phlebotomine sand flies are responsible for the transmission of Leishmania parasites, causing Leishmaniasis. This disease produces a wide spectrum of symptoms, due to a high genetic diversity of parasite strains. In addition to their clonal reproduction, Leishmania can engage in a cryptic sexual cycle resulting in hybrid progeny. Sexual mating is believed to be a major source of Leishmania genetic diversity, which drives changes in tissue tropism, pathology and drug resistance. Experimental generation of hybrids, until recently confined to parasites growing in the sand fly gut, is now possible to achieve in vitro. However, despite the possibility to culture high quantities of parasites, the frequency of hybrids generated in vivo is much higher than in vitro, showing that the vector gut environment is particularly adapted for Leishmania sexual mating. The mechanisms of Leishmania sexual reproduction and the parameters rendering the vector’s gut favorable to this process are currently unknown. I recently observed that pre-exposing parental parasite cultures to Reactive Oxygen Species (ROS) leads to an increased hybrid production in vitro, which led me to hypothesize that ROS, present in large amount in the sand fly gut, could be one of these parameters. Using a dual genetic approach applied on both the parasite and the vector, I aim to decipher the impact of the ROS produced by the sand fly gut cells on the engagement of Leishmania parasites in a sexual reproduction path. This project will generate important knowledge on the Leishmania/sand fly interaction and will set the stage for my future independent research group on the subject.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT PASTEUR · ParisКоординаторФранция