Navarro Yurena, Pérez-Lago Laura, Herranz Marta, Sierra Olalla, Comas Iñaki, Sicilia Javier, Bouza Emilio, García de Viedma Darío
Servicio Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio MarañónMadrid, Spain.
Instituto de Investigación Sanitaria Gregorio MarañónMadrid, Spain.
Front Microbiol. 2017 Apr 24;8:694. doi: 10.3389/fmicb.2017.00694. eCollection 2017.
The role of clonal complexity has gradually been accepted in infection by (MTB), although analyses of this issue are limited. We performed an in-depth study of a case of recurrent MTB infection by integrating genotyping, whole genome sequencing, analysis of gene expression and infectivity in and models. Four different clonal variants were identified from independent intrapatient evolutionary branches. One of the single-nucleotide polymorphisms in the variants mapped in 3R, which encodes a repressor of an operon involved in virulence, and affected expression of the operon. Competitive and co-infection assays revealed higher infective efficiency for one of the clonal variants. A new clonal variant, which had not been observed in the clinical isolates, emerged in the infection assays and showed higher fitness than its parental strain. The analysis of other patients involved in the same transmission cluster revealed new clonal variants acquired through novel evolutionary routes, indicating a high tendency toward microevolution in some strains that is not host-dependent. Our study highlights the need for integration of various approaches to advance our knowledge of the role and significance of microevolution in tuberculosis.
克隆复杂性在结核分枝杆菌（MTB）感染中的作用已逐渐被认可，尽管对此问题的分析有限。我们通过整合基因分型、全基因组测序、基因表达分析以及在小鼠和豚鼠模型中的感染性分析，对一例复发性MTB感染病例进行了深入研究。从独立的患者体内进化分支中鉴定出四种不同的克隆变体。这些变体中的一个单核苷酸多态性位于3R区域，该区域编码一种参与毒力的操纵子的阻遏物，并影响该操纵子的表达。竞争性小鼠和豚鼠共感染试验显示其中一种克隆变体具有更高的感染效率。一种在临床分离株中未观察到的新克隆变体在感染试验中出现，并且显示出比其亲本菌株更高的适应性。对参与同一传播簇的其他患者的分析揭示了通过新的进化途径获得的新克隆变体，表明某些菌株存在高度的微进化趋势，且这种趋势不依赖于宿主。我们的研究强调了整合各种方法以增进我们对微进化在结核病中的作用和意义的认识的必要性。
