Hirsh Aaron E, Tsolaki Anthony G, DeRiemer Kathryn, Feldman Marcus W, Small Peter M
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4871-6. doi: 10.1073/pnas.0305627101. Epub 2004 Mar 23.
Mycobacterium tuberculosis is an important human pathogen in virtually every part of the world. Here we investigate whether distinct strains of M. tuberculosis infect different human populations and whether associations between host and pathogen populations are stable despite global traffic and the convergence of diverse strains of the pathogen in cosmopolitan urban centers. The recent global movement and transmission history of 100 M. tuberculosis isolates was inferred from a molecular epidemiologic study of tuberculosis that spans 12 years. Genetic relationships among these isolates were deduced from the distribution of large genomic deletions, which were identified by DNA microarray and confirmed by PCR and sequence analysis. Phylogenetic analysis of these deletions indicates that they are unique event polymorphisms and that horizontal gene transfer is extremely rare in M. tuberculosis. In conjunction with the epidemiological data, phylogenies reveal three large phylogeographic regions. A host's region of origin is predictive of the strain of tuberculosis he or she carries, and this association remains strong even when transmission takes place in a cosmopolitan urban center outside of the region of origin. Approximate dating of the time since divergence of East Asian and Philippine clades of M. tuberculosis suggests that these lineages diverged centuries ago. Thus, associations between host and pathogen populations appear to be highly stable.
结核分枝杆菌在世界几乎每个角落都是一种重要的人类病原体。在此，我们研究结核分枝杆菌的不同菌株是否感染不同的人类群体，以及尽管存在全球人口流动以及该病原体的不同菌株在国际化城市中心汇聚，宿主与病原体群体之间的关联是否依然稳定。通过一项跨越12年的结核病分子流行病学研究，推断出100株结核分枝杆菌的近期全球传播情况和传播历史。这些菌株之间的遗传关系是根据大型基因组缺失的分布推导出来的，这些缺失通过DNA微阵列鉴定，并通过PCR和序列分析得到证实。对这些缺失的系统发育分析表明，它们是独特事件多态性，并且结核分枝杆菌中的水平基因转移极为罕见。结合流行病学数据，系统发育揭示了三个大的系统地理区域。宿主的起源地区可预测其携带的结核菌株，即使传播发生在起源地区以外的国际化城市中心，这种关联依然很强。对结核分枝杆菌东亚和菲律宾分支分化时间的大致估算表明，这些谱系在几个世纪前就已分化。因此，宿主与病原体群体之间的关联似乎高度稳定。
