Hanekom M, van der Spuy G D, Streicher E, Ndabambi S L, McEvoy C R E, Kidd M, Beyers N, Victor T C, van Helden P D, Warren R M
DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa.
J Clin Microbiol. 2007 May;45(5):1483-90. doi: 10.1128/JCM.02191-06. Epub 2007 Mar 14.
This study aimed to reconstruct the evolutionary history of Beijing strains of Mycobacterium tuberculosis and to test the hypothesis that evolution has influenced the ability of the Beijing strains within the different Beijing sublineages to spread and cause disease. A PCR-based method was used to analyze the genome structure of 40 different loci in 325 Beijing isolates collected from new and retreatment tuberculosis patients from an urban setting and 270 Beijing isolates collected from high-risk tuberculosis patients from a rural setting in the Western Cape, South Africa. The resulting data were subjected to phylogenetic analysis using the neighbor joining algorithm. Phylogenetic reconstructions were highly congruent with the "gold standard" phylogenetic tree based on synonymous single-nucleotide polymorphisms, thereby allowing a prediction of the order in which the evolutionary events had occurred. A total of seven independently evolving Beijing sublineages were identified. Analysis of epidemiological data in relation to the Beijing sublineage suggested an association between recent evolutionary change and frequency of occurrence in an urban population (P<0.001) as well as in the rural population (P<0.001). This concept was further supported by an association between more recently evolved Beijing strains and an increased ability to transmit and to cause disease (odds ratio, 5.82; 95% confidence interval, 3.13 to 10.82 [P<0.001]). An association between Beijing sublineage and demographic and clinical parameters and drug resistance could not be demonstrated. From these data, we suggest that the pathogenic characteristics of Beijing strains are not conserved but rather that strains within individual lineages have evolved unique pathogenic characteristics.
本研究旨在重建结核分枝杆菌北京菌株的进化史，并验证进化影响不同北京亚分支内北京菌株传播和致病能力这一假说。采用基于聚合酶链反应（PCR）的方法，对从城市环境中的新发病例和复治结核病患者收集的325株北京分离株以及从南非西开普农村地区的高危结核病患者收集的270株北京分离株中40个不同位点的基因组结构进行分析。所得数据使用邻接法进行系统发育分析。系统发育重建与基于同义单核苷酸多态性的“金标准”系统发育树高度一致，从而能够预测进化事件发生的顺序。共鉴定出7个独立进化的北京亚分支。对与北京亚分支相关的流行病学数据进行分析，结果表明近期进化变化与城市人群（P<0.001）以及农村人群（P<0.001）中的出现频率之间存在关联。最近进化的北京菌株与传播和致病能力增强之间的关联（优势比为5.82；95%置信区间为3.13至10.82 [P<0.001]）进一步支持了这一概念。未证实北京亚分支与人口统计学和临床参数以及耐药性之间存在关联。根据这些数据，我们认为北京菌株的致病特征并非保守不变，而是各个分支内的菌株已进化出独特的致病特征。
