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LEPVORS SIGNED

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

Total Cost €

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EC-Contrib. €

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Partnership

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Project "LEPVORS" data sheet

The following table provides information about the project.

Coordinator
SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT 

Organization address
address: SOCINSTRASSE 57
city: Basel
postcode: CH-4002
website: www.swisstph.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 153˙916 €
 EC max contribution 153˙916 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-GF
 Starting year 2019
 Duration (year-month-day) from 2019-05-01   to  2022-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT CH (Basel) coordinator 153˙916.00
2    BOARD OF GOVERNORS OF THE COLORADO STATE UNIVERSITY SYSTEM US (FORT COLLINS) partner 0.00

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 Project 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.

 Publications

year authors and title journal last update
List of publications.
2020 Katharina Röltgen, Gerd Pluschke, John Stewart Spencer, Patrick Joseph Brennan, Charlotte Avanzi
The immunology of other mycobacteria: M. ulcerans, M. leprae
published pages: , ISSN: 1863-2297, DOI: 10.1007/s00281-020-00790-4
Seminars in Immunopathology 2020-03-05

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