Whole Genome Sequencing Analysis of Intrapatient Microevolution in Mycobacterium tuberculosis: Potential Impact on the Inference of Tuberculosis Transmission
Whole Genome Sequencing Analysis of Intrapatient Microevolution in Mycobacterium tuberculosis: Potential Impact on the Inference of Tuberculosis Transmission
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DOI：
10.1093/infdis/jit439
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发表时间：
2014-01-01
影响因子：
6.4
通讯作者：
Garcia-de-Viedma, Dario
中科院分区：
文献类型：
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作者：
Perez-Lago, Laura;Comas, Inaki;Garcia-de-Viedma, Dario
背景结核分枝杆菌（Mycobacterium tuberculosis，M.结核病）可能比所考虑的更异质。微进化事件导致的克隆变异体的出现导致种群异质性是一种基本上未被探索的现象。到目前为止，我们只能通过标准的指纹图谱（RFLP和VNTR）对这一现象进行表面分析。在这项研究中，我们应用全基因组测序技术对患者内和患者间的微进化规模进行了更深入的分析。我们发现，患者体内累积的变异量可以与沿着传播链在患者之间观察到的变异量一样高。在肺外和呼吸部位均发现了患者内多样性，这意味着这种变异性可以传播并影响传播事件的推断。研究的一个事件使我们能够跟踪单个菌株的完整过程：（i）患者间的微进化，（ii）患者内的呼吸变异，（iii）在该患者的不同感染部位分离出不同的变体。我们的研究为理解M.结核病在广泛的临床情况下，并提醒有关的困难，建立阈值，以区分相关性的M。结核病流行病学目的。
Background. It has been accepted that the infection by Mycobacterium tuberculosis (M. tuberculosis) can be more heterogeneous than considered. The emergence of clonal variants caused by microevolution events leading to population heterogeneity is a phenomenon largely unexplored. Until now, we could only superficially analyze this phenomenon by standard fingerprinting (RFLP and VNTR).Methods. In this study we applied whole genome sequencing for a more in-depth analysis of the scale of micro evolution both at the intrapatient and interpatient scenarios.Results. We found that the amount of variation accumulated within a patient can be as high as that observed between patients along a chain of transmission. Intrapatient diversity was found both at the extrapulmonary and respiratory sites, meaning that this variability can be transmitted and impact on the inference of transmission events. One of the events studied allowed us to track for a single strain the complete process of (i) interpatient microevolution, (ii) intrapatient respiratory variation, and (iii) isolation of different variants at different infected sites of this patient.Conclusions. Our study adds new data to the understanding of variability in M. tuberculosis in a wide clinical scenario and alerts about the difficulties of establishing thresholds to differentiate relatedness in M. tuberculosis with epidemiological purposes.