Frontiers in Microbiology publish this investigation article

April 24^th, 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.

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

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

	Servicio 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.
	Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP). Instituto de Salud Carlos III (ISCIII).
	CEI Campus Moncloa.
	Servicio de Micobacterias (MYC). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).
	Unidad Mixta y Genómica y Salud Pública. Fundació per al Foment de la Investigació Sanitària i Biomèdica (FISABIO). Universitat de València (UV).
	Departamento de Medicina. Facultad de Medicina. Universidad Complutense (UCM).