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Linking within host and between host evolution of multidrug resistant Mycobacter...

Linking within host and between host evolution of multidrug resistant Mycobacterium tuberculosis Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is the main cause of human deaths due to infection in general, and to antimicrobial resistance in particular. Little is known on the within-host evolution... ver más

31/01/2026

SWISS TPH SWISS TR...

3M€

Presupuesto del proyecto: 3M€

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.

Ver 3 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-07-24

ERC-2019-ADG: ERC Advanced Grant

I+D

Cerrada hace 5 años

0% 100% 100%

Información adicional privada

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

3 Participantes

SWISS TPH SWISS TROPICAL AND...

1.93M€ | Lider

NATIONAL CENTER FOR TUBERCUL...

NCTLD

573.38K€ | Participante

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Duración del proyecto: 66 meses Fecha Inicio: 2020-07-24
Fecha Fin: 2026-01-31

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 3M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is the main cause of human deaths due to infection in general, and to antimicrobial resistance in particular. Little is known on the within-host evolution of Mtb. Theory predicts that in chronic infections like TB, short-sighted evolution operates in the light of a trade-off between virulence and transmission. This trade-off is particularly relevant in the context of drug resistance, given the fitness costs of resistance. However, the role of short-sighted evolution in TB has never been explored empirically. Theory and model systems further predict that phenotypic drug tolerance facilitates the emergence of drug resistance, but the relevance of phenotypic drug tolerance for drug resistance evolution in the clinic has not been established for TB or any other bacterial disease. To address these and related questions, I propose to build on my recent work on the transmission of drug-resistant Mtb with a new focus on the within-patient evolution of drug-resistant Mtb and its link to between-patient evolution during transmission. Specifically, I shall: 1) Define the genomic characteristics and evolutionary forces shaping multidrug-resistant Mtb populations in individual patients over time and across different body compartments; 2) Compare the genomic and phenotypic properties of multidrug-resistant Mtb populations in individual patients to those circulating within the corresponding patient population; 3) Determine the effect of suboptimal patient treatment and phenotypic drug tolerance on drug resistance evolution in Mtb inside patients. By combining population genomics of Mtb sampled sequentially and from surgical specimens with experimental evolution and phenotypic characterization of clinical and experimentally evolved strains, this project will generate new insights relevant to both basic science and global public health.

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