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dc.contributor.authorNavarro, Yurena
dc.contributor.authorPérez-Lago, Laura
dc.contributor.authorHerranz, Marta
dc.contributor.authorSierra, Olalla
dc.contributor.authorComas, Iñaki
dc.contributor.authorSicilia, Javier
dc.contributor.authorBouza, Emilio
dc.contributor.authorGarcía de Viedma, Darío
dc.identifier.citationFront Microbiol.2017;(8):694
dc.description.abstractThe 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.
dc.subjectMycobacterium tuberculosis
dc.subjectfunctional analysis
dc.subjectin vitro infections
dc.subjectin vivo infections
dc.subjectwhole genome sequencing
dc.titleIn-Depth Characterization and Functional Analysis of Clonal Variants in a Mycobacterium tuberculosis Strain Prone to Microevolution.
dc.identifier.journalFrontiers in microbiology
dc.pubmedtypeJournal Article
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. General U. Gregorio Marañón > Artículos

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