Robert Koch Institut, Wernigerode, Germany.
PLoS Pathog. 2010 Apr 8;6(4):e1000855. doi: 10.1371/journal.ppat.1000855.
Due to the lack of fossil evidence, the timescales of bacterial evolution are largely unknown. The speed with which genetic change accumulates in populations of pathogenic bacteria, however, is a key parameter that is crucial for understanding the emergence of traits such as increased virulence or antibiotic resistance, together with the forces driving pathogen spread. Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of hospital-acquired infections. We have investigated an MRSA strain (ST225) that is highly prevalent in hospitals in Central Europe. By using mutation discovery at 269 genetic loci (118,804 basepairs) within an international isolate collection, we ascertained extremely low diversity among European ST225 isolates, indicating that a recent population bottleneck had preceded the expansion of this clone. In contrast, US isolates were more divergent, suggesting they represent the ancestral population. While diversity was low, however, our results demonstrate that the short-term evolutionary rate in this natural population of MRSA resulted in the accumulation of measurable DNA sequence variation within two decades, which we could exploit to reconstruct its recent demographic history and the spatiotemporal dynamics of spread. By applying Bayesian coalescent methods on DNA sequences serially sampled through time, we estimated that ST225 had diverged since approximately 1990 (1987 to 1994), and that expansion of the European clade began in 1995 (1991 to 1999), several years before the new clone was recognized. Demographic analysis based on DNA sequence variation indicated a sharp increase of bacterial population size from 2001 to 2004, which is concordant with the reported prevalence of this strain in several European countries. A detailed ancestry-based reconstruction of the spatiotemporal dispersal dynamics suggested a pattern of frequent transmission of the ST225 clone among hospitals within Central Europe. In addition, comparative genomics indicated complex bacteriophage dynamics.
由于缺乏化石证据，细菌进化的时间尺度在很大程度上是未知的。然而，在致病性细菌群体中遗传变化的积累速度是一个关键参数，对于理解增加的毒力或抗生素耐药性等特征的出现以及驱动病原体传播的力量至关重要。耐甲氧西林金黄色葡萄球菌（MRSA）是医院获得性感染的常见原因。我们研究了一种在中欧医院中高度流行的 MRSA 菌株（ST225）。通过在国际分离株集合中 269 个遗传基因座（118804 个碱基对）进行突变发现，我们确定了欧洲 ST225 分离株之间的极低多样性，表明在此克隆扩展之前，最近发生了种群瓶颈。相比之下，美国分离株的多样性更高，这表明它们代表了祖先种群。然而，尽管多样性较低，但我们的结果表明，在这个 MRSA 的自然种群中，短期进化率导致在二十年的时间内积累了可衡量的 DNA 序列变异，我们可以利用这些变异来重建其最近的人口历史和传播的时空动态。通过对随时间顺序采样的 DNA 序列应用贝叶斯合并方法，我们估计 ST225 自大约 1990 年（1987 年至 1994 年）以来已经分化，并且欧洲分支的扩展始于 1995 年（1991 年至 1999 年），在新克隆被识别之前的几年。基于 DNA 序列变异的人口分析表明，细菌种群数量从 2001 年到 2004 年急剧增加，这与该菌株在几个欧洲国家的报告流行率相符。对时空扩散动态的详细基于祖先的重建表明，ST225 克隆在中欧医院之间频繁传播。此外，比较基因组学表明了复杂的噬菌体动态。
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