Servicio Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
J Infect Dis. 2014 Jan 1;209(1):98-108. doi: 10.1093/infdis/jit439. Epub 2013 Aug 14.
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).
In this study we applied whole genome sequencing for a more in-depth analysis of the scale of microevolution both at the intrapatient and interpatient scenarios.
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.
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.
已经公认分枝杆菌（M. tuberculosis）的感染比之前认为的更为复杂多样。由于微进化事件导致的种群异质性而出现的克隆变体的出现，是一个尚未得到充分探索的现象。到目前为止，我们只能通过标准的指纹图谱（RFLP 和 VNTR）对这种现象进行表面分析。
在这项研究中，我们应用全基因组测序来更深入地分析患者内和患者间微进化的规模。
我们发现，患者内积累的变异量可以高达传播链上患者间的变异量。在肺外和呼吸道部位都发现了患者内的多样性，这意味着这种可变性可以传播并影响对传播事件的推断。我们研究的一个事件使我们能够跟踪一个单一菌株，了解其在（i）患者间微进化、（ii）患者内呼吸道变异、（iii）患者不同感染部位不同变异株的分离等方面的完整过程。
我们的研究为分枝杆菌在广泛临床场景中的变异性提供了新的数据，并提醒人们在分枝杆菌的流行病学目的方面建立区分相关性的阈值存在困难。
