Project description DEENESFRITPL The pathogen genetics behind the clinical forms of leprosy Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis, which are difficult to study as they cannot be cultivated in the laboratory. The recent sequencing of different bacterial isolates has identified hypermutated genes with potential roles in drug resistance and species adaptation. The scope of the EU-funded LEPVORS project is to associate these genetic changes with clinical phenotype and drug resistance. Moreover, using recent molecular advances such as next generation sequencing, researchers will study additional strains isolated from rarer clinical forms of leprosy. Results will provide unprecedented insight into the biology and host adaptation of the causative agent of leprosy. Show the project objective Hide the project objective Objective 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. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancenatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsgenomes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-GF - Global Fellowships Coordinator SCHWEIZERISCHES TROPEN UND PUBLIC HEALTH INSTITUT Net EU contribution € 153 916,20 Address Kreuzstrasse 2 4123 Allschwil Switzerland See on map Region Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Landschaft Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. BOARD OF GOVERNORS OF THE COLORADO STATE UNIVERSITY SYSTEM United States Net EU contribution € 0,00 Address Colorado state university 80523 2001 Fort collins See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 93 828,84
