Skip to main content

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.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /medical and health sciences/health sciences/public and environmental health/epidemics prevention/immunisation
  • /natural sciences/biological sciences/microbiology/bacteriology
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance
  • /natural sciences/biological sciences/genetics and heredity/mutation

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
Address
Socinstrasse 57
CH-4002 Basel
Switzerland
Activity type
Research Organisations
EU contribution
€ 153 916,20

Partners (1)

BOARD OF GOVERNORS OF THE COLORADO STATE UNIVERSITY SYSTEM
United States
Address
Colorado State University
80523 2001 Fort Collins
Activity type
Higher or Secondary Education Establishments