WHO Supranational TB Reference Laboratory, TB and Mycobacteria Unit, Institut Pasteur de la Guadeloupe, Abymes, France.
PLoS One. 2012;7(9):e41991. doi: 10.1371/journal.pone.0041991. Epub 2012 Sep 11.
Multiple-locus variable-number tandem repeat analysis (MLVA) is useful to establish transmission routes and sources of infections for various microorganisms including Mycobacterium tuberculosis complex (MTC). The recently released SITVITWEB database contains 12-loci Mycobacterial Interspersed Repetitive Units--Variable Number of Tandem DNA Repeats (MIRU-VNTR) profiles and spoligotype patterns for thousands of MTC strains; it uses MIRU International Types (MIT) and Spoligotype International Types (SIT) to designate clustered patterns worldwide. Considering existing doubts on the ability of spoligotyping alone to reveal exact phylogenetic relationships between MTC strains, we developed a MLVA based classification for MTC genotypic lineages. We studied 6 different subsets of MTC isolates encompassing 7793 strains worldwide. Minimum spanning trees (MST) were constructed to identify major lineages, and the most common representative located as a central node was taken as the prototype defining different phylogenetic groups. A total of 7 major lineages with their respective prototypes were identified: Indo-Oceanic/MIT57, East Asian and African Indian/MIT17, Euro American/MIT116, West African-I/MIT934, West African-II/MIT664, M. bovis/MIT49, M.canettii/MIT60. Further MST subdivision identified an additional 34 sublineage MIT prototypes. The phylogenetic relationships among the 37 newly defined MIRU-VNTR lineages were inferred using a classification algorithm based on a bayesian approach. This information was used to construct an updated phylogenetic and phylogeographic snapshot of worldwide MTC diversity studied both at the regional, sub-regional, and country level according to the United Nations specifications. We also looked for IS6110 insertional events that are known to modify the results of the spoligotyping in specific circumstances, and showed that a fair portion of convergence leading to the currently observed bias in phylogenetic classification of strains may be traced back to the presence of IS6110. These results shed new light on the evolutionary history of the pathogen in relation to the history of peopling and human migration.
多位点可变数目串联重复分析（MLVA）对于建立包括结核分枝杆菌复合体（MTC）在内的各种微生物的传播途径和感染源非常有用。最近发布的 SITVITWEB 数据库包含了数千株 MTC 菌株的 12 个位点分枝杆菌散布重复单位 - 可变数目的串联 DNA 重复（MIRU-VNTR）图谱和 spoligotype 模式；它使用 MIRU 国际类型（MIT）和 spoligotype 国际类型（SIT）来指定全球范围内的聚类模式。鉴于 spoligotyping 单独用于揭示 MTC 菌株之间的确切进化关系存在现有疑问，我们开发了一种基于 MLVA 的 MTC 基因型谱系分类方法。我们研究了涵盖全球 7793 株 MTC 分离株的 6 个不同子集。构建最小生成树（MST）以识别主要谱系，并将位于中央节点的最常见代表作为定义不同进化群的原型。确定了 7 个主要谱系及其各自的原型：印度洋/ MIT57、东亚和非洲印度/ MIT17、欧美/ MIT116、西非-I/ MIT934、西非-II/ MIT664、牛分枝杆菌/ MIT49、M.canettii/ MIT60。进一步的 MST 细分确定了另外 34 个亚谱系 MIT 原型。使用基于贝叶斯方法的分类算法推断 37 个新定义的 MIRU-VNTR 谱系之间的进化关系。根据联合国的规范，根据区域、次区域和国家层面研究了全球 MTC 多样性的信息，用于构建最新的 MTC 多样性进化和系统地理快照。我们还寻找了已知在特定情况下会改变 spoligotyping 结果的 IS6110 插入事件，并表明导致目前观察到的菌株进化分类偏差的相当一部分收敛可以追溯到 IS6110 的存在。这些结果为病原体的进化历史与人口和人类迁移的历史之间的关系提供了新的认识。
