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Identification and characterization of new drug resistance and host adaptation m...

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

31/01/2022

SWISS TPH SWISS TR...

154K€

Presupuesto del proyecto: 154K€

Líder del proyecto

SCHWEIZERISCHES TROPEN UND PUBLIC HEALTH INST... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-01-31

MSCA-IF-2018: Individual Fellowships

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No hay información privada compartida para este proyecto. Habla con el coordinador.

3 Participantes

SWISS TPH SWISS TROPICAL AND...

153.92K€ | Lider

BOARD OF GOVERNORS OF THE CO...

COLORADO STATE UNIVERSITY

93.83K€ | Participante

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Duración del proyecto: 33 meses Fecha Inicio: 2019-04-24
Fecha Fin: 2022-01-31

Líder del proyecto

SCHWEIZERISCHES TROPEN UND PUBLIC HEALTH INST... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 154K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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