Send to

Choose Destination
Front Microbiol. 2018 Jan 19;8:2661. doi: 10.3389/fmicb.2017.02661. eCollection 2017.

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts.

Author information

Servicio Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Childhood Tuberculosis Department, Centre of Tuberculosis and Lung Diseases, Riga East University Hospital, Riga, Latvia.
Latvian Biomedical Research and Study Centre, Riga, Latvia.
Department of Infectology and Dermatology, Riga Stradinš University, Riga, Latvia.
Unidad Mixta Genómica y Salud, Centro Superior de Investigación en Salud Pública (FISABIO)-Universitat de València, Valencia, Spain.
Servicio de Microbiología, Complejo Hospitalario Torrecárdenas, Almería, Spain.
Servei de Vigilància Epidemiològica i Resposta a Emergències de Salut Pública al Vallès Occidental i Vallès Oriental, Subdirecció General de Vigilància i Resposta a Emergències de Salut Pública, Agència de Salut Pública de Catalunya, Barcelona, Spain.
Servicio de Laboratorio, Institut d'Investigació i Innovació Parc Taulí, I3PT Parc Taulí Hospital Universitari, Universitat Autònoma de Barcelona, Barcelona, Spain.
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, Spain.
CIBER en Epidemiología y Salud Pública, Madrid, Spain.
Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.


Background:Mycobacterium tuberculosis (MTB) has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS) in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs) between isolates. Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts. Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission. Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed. Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.


SNPs; microevolution; tuberculosis; variability; whole genome sequencing

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center