H2020Индивидуална стипендия2019–2022

LEPVORS · Identification and characterization of new drug resistance and host adaptation mechanisms in Mycobacterium leprae

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

Период: 2019-05-01 → 2022-01-31
Финансиране от ЕС: 153 916 €
Участници: 2
Схема: MSCA-IF-GF

Линиите свързват координатора с партньорите.

Накратко на български

Генетичните промени в бактерията Mycobacterium leprae се анализират, за да се разбере как тя се адаптира към организма и развива устойчивост към лекарства. Това е важно, защото помага за разясняване на механизмите, които застрашават елиминирането на проказа.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Identification and characterization of new drug resistance and host adaptation mechanisms in Mycobacterium leprae

Leprosy is caused by Mycobacterium leprae, which is challenging to study as it cannot be cultivated in the laboratory. Leprosy elimination is threatened by the emergency of drug resistance and our poor knowledge of the current drug resistance mechanisms and physiopathological bacterial markers. The recent sequencing of different bacterial isolates has identified hypermutated genes with potential drug resistance and species adaptation roles. The EU-funded LEPVORS project's scope is to characterise and associate these genetic changes with clinical phenotype, drug resistance and host response.

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

Цел на проекта

Leprosy is a multiform infection caused by Mycobacterium leprae, an uncultivable bacLeprosy is a slow and chronic infection caused by Mycobacterium leprae. Recent advances in the next generation sequencing offer a new possibility to study the physiopathology of M. leprae, an uncultivable bacteria on anexic media. In 2018, the comparative analysis of 154 M. leprae genomes from 25 countries identified three hypermutated genes including two (ribD and fadD9) probably associated with drug-resistant and the most mutated one being ml0411 with a potential role in host adaptation. In a mycobacterial species, like M. leprae, with such a reduced number of coding genes, it is reasonable to assume that this high rate of mutations probably led to the modification of essential biological functions. In addition, the recent development of more efficient molecular tools can now help to obtain the whole genome sequencing of the strain from the low representative forms of the disease. This could help to identify more of these highly mutated genes and establish a link between the pathogen genetic and the clinical disease outcome. This project proposes to functionally characterize some of the mutations identified but also to identify new candidates which could be linked with differences in host phenotype. The study has three specific aims: Specific aim 1 will focus on potential new genes involved in M. leprae drug resistance. Using surrogate mycobacteria such as M. tuberculosis and M. haemophilum, we will test the drug susceptibility of mutated strains in fadD9 and ribD compared to wild-type strains. In specific aim 2, we will investigate the role of ml0411 and mutated version on the host innate immune response modulation In specific aim 3, we will focus on the whole genome sequencing of M. leprae strain from the less represented clinical form of leprosy, the tuberculoid pole to identify new genetic differences in the bacteria which could be associated with different host phenotypes.

Оригинален текст от CORDIS (на английски).

Участници

SCHWEIZERISCHES TROPEN UND PUBLIC HEALTH INSTITUT · AllschwilКоординаторШвейцария
BOARD OF GOVERNORS OF THE COLORADO STATE UNIVERSITY SYSTEM · Fort CollinsСъединени щати