CORDIS
EU research results

CORDIS

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

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

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.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Coordinator

SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT

Address

Socinstrasse 57
Ch-4002 Basel

Switzerland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 153 916,20

Partners (1)

Sort alphabetically

Expand all

BOARD OF GOVERNORS OF THE COLORADO STATE UNIVERSITY SYSTEM

Project information

Grant agreement ID: 845479

Status

Ongoing project

  • Start date

    1 May 2019

  • End date

    31 January 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 153 916,20

  • EU contribution

    € 153 916,20

Coordinated by:

SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT

Switzerland