Enright Mark C, Spratt Brian G
Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
Microbiology (Reading). 1998 Nov;144 ( Pt 11):3049-3060. doi: 10.1099/00221287-144-11-3049.
The population biology of Streptococcus pneumoniae is poorly understood. Most of the important issues could be addressed by the molecular characterization of large, well sampled populations from carriage and from the different manifestations of pneumococcal disease. The authors have therefore developed a pneumococcal multilocus sequence typing scheme and database by sequencing approximately 450 bp fragments of seven housekeeping loci from 295 isolates. The combination of alleles at the seven loci provided an allelic profile, or sequence type (ST), and the relatedness between isolates was obtained by constructing a dendrogram from the matrix of pairwise differences between STs. The typing scheme was validated using pneumococci of known genetic relatedness and could resolve >6 billion STs. Among 274 isolates from recent cases of invasive pneumococcal disease in eight countries, 143 STs were resolved, but 12 STs contained at least five isolates (range 5-21 isolates). The repeated recovery of indistinguishable isolates from invasive disease in different countries implies that these STs define strains with an increased capacity to cause invasive disease. The relationship between STs and serotypes suggested that, in the longer term, capsular genes have been distributed horizontally within the pneumococcal population, but in the short term, expansion of clones occurs with only occasional changes of serotype. The multilocus sequence typing scheme provides a powerful new approach to the characterization of pneumococci, since it provides molecular typing data that are electronically portable between laboratories, and which can be used to probe aspects of the population and evolutionary biology of these organisms. A Web site for the molecular characterization of pneumococci by MLST is available (http ://mlst.zoo.ox.ac.uk).
肺炎链球菌的群体生物学目前了解甚少。大部分重要问题可通过对来自携带状态及肺炎球菌疾病不同表现形式的、采样充分的大群体进行分子特征分析来解决。因此，作者通过对295株分离株的7个管家基因座的约450 bp片段进行测序，开发了一种肺炎球菌多位点序列分型方案及数据库。7个基因座上等位基因的组合提供了一个等位基因谱，即序列型（ST），通过根据ST之间的成对差异矩阵构建树状图来获得分离株之间的亲缘关系。该分型方案使用已知遗传相关性的肺炎球菌进行了验证，可分辨超过60亿种ST。在来自8个国家近期侵袭性肺炎球菌疾病病例的274株分离株中，分辨出了143种ST，但有12种ST包含至少5株分离株（范围为5 - 21株）。在不同国家的侵袭性疾病中反复分离出难以区分的分离株，这意味着这些ST定义了具有更强侵袭性疾病致病能力的菌株。ST与血清型之间的关系表明，从长远来看，荚膜基因已在肺炎球菌群体中水平分布，但在短期内，克隆的扩张仅伴随着血清型的偶尔变化。多位点序列分型方案为肺炎球菌的特征分析提供了一种强大的新方法，因为它提供了可在实验室之间电子传输的分子分型数据，并且可用于探究这些生物体群体和进化生物学的各个方面。现有一个通过MLST对肺炎球菌进行分子特征分析的网站（http ://mlst.zoo.ox.ac.uk）。
