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In-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution

Frontiers in Microbiology publish this investigation article

April 24th, 2017

The role of clonal complexity has gradually been accepted in infection by Mycobacterium tuberculosis (MTB), although analyses of this issue are limited. We performed an in-depth study of a case of recurrent MTB infection by integrating genotyping, whole genome sequencing, analysis of gene expression and infectivity in in vitro and in vivo models. Four different clonal variants were identified from independent intrapatient evolutionary branches. One of the single-nucleotide polymorphisms in the variants mapped in mce3R, which encodes a repressor of an operon involved in virulence, and affected expression of the operon. Competitive in vivo and in vitro co-infection assays revealed higher infective efficiency for one of the clonal variants. A new clonal variant, which had not been observed in the clinical isolates, emerged in the infection assays and showed higher fitness than its parental strain. The analysis of other patients involved in the same transmission cluster revealed new clonal variants acquired through novel evolutionary routes, indicating a high tendency toward microevolution in some strains that is not host-dependent. Our study highlights the need for integration of various approaches to advance our knowledge of the role and significance of microevolution in tuberculosis




Navarro Y., Perez-Lago L., Herranz M., Sierra O., Comas I., Sicilia J., Bouza E. and Garcia de Viedma D.




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In-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution

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In-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution



Participants:

Comunidad de MadridServicio de Microbiología y Enfermedades Infecciosas. Instituto de Investigación Sanitaria Gregorio Marañón (IISGM). Unidad de Medicina y Cirugía Experimental. Hospital General Universitario Gregorio Marañón. Salud Madrid. Comunidad de Madrid.

Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP). Instituto de Salud Carlos III (ISCIII).

CEI Campus MoncloaCEI Campus Moncloa.

Universidad ComplutenseServicio de Micobacterias (MYC). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Universitat de ValènciaUnidad Mixta y Genómica y Salud Pública. Fundació per al Foment de la Investigació Sanitària i Biomèdica (FISABIO). Universitat de València (UV).

Universidad ComplutenseDepartamento de Medicina. Facultad de Medicina. Universidad Complutense (UCM).







Frontiers in Microbiology
FACTOR YEAR Q
4.109 2017

NLMID: 101548977

PMID: 28484440

ISSN: 1664-302X



TITLE: In-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution


JOURNAL: Front Microbiol


NUMERACIÓN: 8:694


AÑO: 2017


PUBLISHER: Frontiers Research Foundation


AUTHORS: Navarro Y., Perez-Lago L., Herranz M., Sierra O., Comas I., Sicilia J., Bouza E. and Garcia de Viedma D.


DOI: https://doi.org/10.3389/fmicb.2017.00694


CITE THIS PUBLICATION:

Navarro Y., Perez-Lago L., Herranz M., Sierra O., Comas I., Sicilia J., Bouza E. and Garcia de Viedma D. In-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution. Frontiers in Microbiology. 8:694. 2017. (A). ISSN: 1664-302X. DOI: 10.3389/fmicb.2017.00694


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