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:
Inst Biomed Valencia IBV CSIC, Valencia, Spain
Shubladze, N:
Natl Ctr TB & Lung Dis Georgia, Tbilisi, Georgia
Khurtsilava, I:
Natl Ctr TB & Lung Dis Georgia, Tbilisi, Georgia
Avaliani, Z:
Natl Ctr TB & Lung Dis Georgia, Tbilisi, Georgia
Bablishvili, N:
Natl Ctr TB & Lung Dis Georgia, Tbilisi, Georgia
Torres-Puente, M:
Inst Biomed Valencia IBV CSIC, Valencia, Spain
Villamayor, L:
FISABIO Publ Hlth, Valencia, Spain
Gabrielian, A:
NIAID, NIH, US Dept HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA
Rosenthal, A:
NIAID, NIH, US Dept HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA
:
Fundacio Inst Germans Trias & Pujol IGTP, Barcelona, Spain
Univ Autonoma Barcelona UAB, Barcelona, Spain
CIBER Resp Dis, Madrid, Spain
Gagneux, S:
Swiss Trop & Publ Hlth Inst, Basel, Switzerland
Univ Basel, Basel, Switzerland
Kempker, RR:
Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA
Vashakidze, S:
Natl Ctr TB & Lung Dis Georgia, Tbilisi, Georgia
Comas, I:
Inst Biomed Valencia IBV CSIC, Valencia, Spain
CIBER Epidemiol & Publ Hlth, Madrid, Spain
Green Published, gold
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