Navarro Yurena, Romero Beatriz, Bouza Emilio, Domínguez Lucas, de Juan Lucía, García-de-Viedma Darío
Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades respiratorias, CIBERES, Spain; CEI Campus Moncloa, UCM-UPM, Madrid, Spain; Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Universidad Complutense de Madrid, Madrid, Spain.
CEI Campus Moncloa, UCM-UPM, Madrid, Spain; Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Universidad Complutense de Madrid, Madrid, Spain.
Vet Microbiol. 2016 Feb 1;183:97-102. doi: 10.1016/j.vetmic.2015.11.032. Epub 2015 Nov 27.
Various studies have analyzed microevolution events leading to the emergence of clonal variants in human infections by Mycobacterium tuberculosis. However, microevolution events in animal tuberculosis remain unknown. We performed a systematic analysis of microevolution events in eight herds that were chronically infected by Mycobacterium bovis for more than 12 months. We analyzed 88 animals using a systematic screening procedure based on discriminatory MIRU-VNTR genotyping at sequential time points during the infection. Microevolution was detected in half of the herds studied. Emergence of clonal variants did not require long infection periods or a high number of infected animals in the herd. Microevolution was not restricted to strains from specific spoligotypes, and the subtle variations detected involved different MIRU loci. The genetic locations of the subtle genotypic variations recorded in the clonal variants indicated potential functional significance. This finding was consistent with the dynamics of some clonal variants, which outcompeted the original strains, suggesting an advantageous phenotype. Our data constitute a first step in defining the thresholds of variability to be tolerated in molecular epidemiology studies of M. bovis. We could therefore ensure that related clonal variants emerging as a result of microevolution events are not going to be misinterpreted as unrelated isolates.
多项研究分析了导致结核分枝杆菌在人类感染中出现克隆变体的微观进化事件。然而，动物结核病中的微观进化事件仍不为人知。我们对8个长期感染牛分枝杆菌超过12个月的牛群中的微观进化事件进行了系统分析。我们在感染期间的连续时间点，采用基于鉴别性MIRU-VNTR基因分型的系统筛选程序，对88头动物进行了分析。在所研究的一半牛群中检测到了微观进化。克隆变体的出现并不需要很长的感染期或牛群中有大量感染动物。微观进化并不局限于特定间隔寡核苷酸分型的菌株，检测到的细微变异涉及不同的MIRU位点。克隆变体中记录的细微基因型变异的基因位置表明了潜在的功能意义。这一发现与一些克隆变体的动态变化一致，这些克隆变体胜过了原始菌株，表明具有有利的表型。我们的数据是确定牛分枝杆菌分子流行病学研究中可容忍变异性阈值的第一步。因此，我们可以确保因微观进化事件而出现的相关克隆变体不会被误判为不相关的分离株。
