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Inferring Epidemiology and Microevolution of Mycobacterium Tuberculosis Strains from Deep-Sequencing Data of Patient Samples
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Inferring Epidemiology and Microevolution of Mycobacterium Tuberculosis Strains from Deep-Sequencing Data of Patient Samples
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Inferring Epidemiology and Microevolution of Mycobacterium Tuberculosis Strains from Deep-Sequencing Data of Patient Samples
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Dissertation
Inferring Epidemiology and Microevolution of Mycobacterium Tuberculosis Strains from Deep-Sequencing Data of Patient Samples
2017
Overview
Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis is an infectious disease that remains a global public health problem where approximately one-third of the world population have been at least in contact and is latently infected with.Whole genome sequencing has revolutionized the investigation of mycobacterial genomes. The application of this technology has provided innovative understandings into the evolution of the Mycobacterium tuberculosis due to recent studies reporting conflicting findings on its genomic stability, particularly during the evolution of drug resistance in modern lineages.To address this question we focused on understanding the genotypic and epidemiological factors that influence the spread and fitness of this bacterium by analyzing deep –sequencing data of 85 patient samples from Central Asia. Samples were part of a larger study of 399 clinical isolates of newly diagnosed patients with pulmonary TB collected between 2012 and 2013 at the NCTLD in Tbilisi, Georgia.All the samples were mapped against H37Rv strain. We focused on single-nucleotide polymorphisms to reconstruct models for molecular evolution, using Maximum Likelihood and Bayesian Inference methods. 84% of our population belongs to the Beijing lineage, associated with the massive spread of multidrug-resistant strains. Relationship between mutations on rpoB and rpoC were associated with drug resistance to rifampicin and mutations on pncA region also demonstrated to be related with drug resistance to pyrazinamide.Furthermore we found that the amount of variation accumulated within a patient can be as high as that observed between patients along, what we assume to be, a chain of transmission. Intrapatient diversity was found in all of the follow up patients.Our study adds new data to the understandings of the variability among Mycobacterium tuberculosisstrains in an intra and interpatient microevolution scenario.
