Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections
Por:
Moreno-Molina M, Shubladze N, Khurtsilava I, Avaliani Z, Bablishvili N, Torres-Puente M, Villamayor L, Gabrielian A, Rosenthal A, Vilaplana C, Gagneux S, Kempker RR, Vashakidze S and Comas I
Publicada:
11 may 2021
Ahead of Print:
11 may 2021
Resumen:
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.
Filiaciones:
Moreno-Molina M:
Instituto de Biomedicina de Valencia IBV-CSIC, Valencia, Spain
Shubladze N:
National Center for Tuberculosis and Lung Diseases of Georgia, Tbilisi, Georgia
Khurtsilava I:
National Center for Tuberculosis and Lung Diseases of Georgia, Tbilisi, Georgia
Avaliani Z:
National Center for Tuberculosis and Lung Diseases of Georgia, Tbilisi, Georgia
Bablishvili N:
National Center for Tuberculosis and Lung Diseases of Georgia, Tbilisi, Georgia
:
Instituto de Biomedicina de Valencia IBV-CSIC, Valencia, Spain
:
FISABIO Public Health, Valencia, Spain
Gabrielian A:
National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Maryland, USA
Rosenthal A:
National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Maryland, USA
Vilaplana C:
Fundació Institut Germans Trias i Pujol (IGTP), Barcelona, Spain
Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
CIBER of Respiratory Diseases, Madrid, Spain
Gagneux S:
Swiss Tropical and Public Health Institute, Basel, Switzerland
University of Basel, Basel, Switzerland
Kempker RR:
Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, USA
Vashakidze S:
National Center for Tuberculosis and Lung Diseases of Georgia, Tbilisi, Georgia
:
Instituto de Biomedicina de Valencia IBV-CSIC, Valencia, Spain.
CIBER in Epidemiology and Public Health, Madrid, Spain.
gold, Green Published, Green Accepted
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