Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections
Moreno-Molina, Miguel (Instituto de Biomedicina de Valencia (IBV-CSIC))
Shubladze, Natalia (National Center for Tuberculosis and Lung Diseases of Georgia)
Khurtsilava, Iza (National Center for Tuberculosis and Lung Diseases of Georgia)
Avaliani, Zaza (National Center for Tuberculosis and Lung Diseases of Georgia)
Bablishvili, Nino (National Center for Tuberculosis and Lung Diseases of Georgia)
Torres-Puente, Manuela (Instituto de Biomedicina de Valencia (IBV-CSIC))
Villamayor, Luis (FISABIO Public Health)
Gabrielian, Andrei (National Institutes of Health. Department of Health and Human Services (Estats Units d'Amèrica))
Rosenthal, Alex (National Institutes of Health. Department of Health and Human Services (Estats Units d'Amèrica))
Vilaplana, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Gagneux, Sebastien (University of Basel)
Kempker, Russell R. (Emory University School of Medicine. Department of Medicine)
Vashakidze, Sergo (National Center for Tuberculosis and Lung Diseases of Georgia)
Comas, I (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples. Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. Here, Moreno-Molina et al. analyse sputum and surgical resections from tuberculosis patients, showing that the magnitude of polyclonal infections can be underestimated when only testing sputum samples.
Grants:	Ministerio de Economía y Competitividad SAF2016-77346-R Ministerio de Economía y Competitividad PID2019-104477RB-I00 Ministerio de Economía y Competitividad PI16/01511 European Commission 638553
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Bacterial genomics ; Clinical microbiology ; Pathogens ; Tuberculosis
Published in:	Nature communications, Vol. 12 (may 2021) , ISSN 2041-1723

DOI: 10.1038/s41467-021-22705-z
PMID: 33976135

11 p, 3.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles