Feil Edward J, Cooper Jessica E, Grundmann Hajo, Robinson D Ashley, Enright Mark C, Berendt Tony, Peacock Sharon J, Smith John Maynard, Murphy Michael, Spratt Brian G, Moore Catrin E, Day Nicholas P J
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
J Bacteriol. 2003 Jun;185(11):3307-16. doi: 10.1128/JB.185.11.3307-3316.2003.
Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable "core" genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.
金黄色葡萄球菌是一种重要的人类病原体，由于抗生素耐药性克隆的出现和传播，尤其是在医院环境中，它给公共卫生带来的负担日益加重。尽管如此，关于该物种的进化和群体生物学的一些基本问题，特别是同源重组的程度和影响，仍然没有答案。我们通过分析从334株金黄色葡萄球菌的多位点序列分型（MLST）鉴定中获得的序列数据来解决这些问题，这些菌株是在有限的时间跨度内从一个明确界定的群体中分离出来的。我们发现，从携带者分离出的菌株与从侵袭性疾病患者分离出的菌株之间，多位点基因型的分布没有显著差异；因此，从MLST数据（该数据可索引稳定“核心”基因组内的变异）中没有证据表明该病原体存在高毒力克隆。在克隆多样化过程中对MLST位点的序列变化进行检查发现，点突变产生新等位基因的频率至少比重组高15倍。这与自然可转化的物种脑膜炎奈瑟菌和肺炎链球菌形成对比，在这两种细菌中，等位基因通过重组改变的频率比通过突变改变的频率高5至10倍。然而，系统发育分析表明，从长期来看，同源重组确实对该物种的进化有贡献。最后，我们注意到，与属于不同克隆复合体的分离株相比，属于同一克隆复合体的分离株之间非同义替换明显过多，这表明通过纯化选择去除有害突变的速度可能相对较慢。
