Department of Statistics, University of Oxford, Oxford, Oxfordshire, United Kingdom.
PLoS One. 2013 May 1;8(5):e61319. doi: 10.1371/journal.pone.0061319. Print 2013.
Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus.
We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA).
This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease.
金黄色葡萄球菌是导致与医疗保健相关的死亡的主要原因，但与许多重要的细菌病原体一样，它也是正常人体菌群的常见组成部分。大约三分之一的健康成年人是携带者。最近的证据表明，金黄色葡萄球菌在鼻腔携带过程中的进化可能与侵袭性疾病的进展有关。然而，为了更好地理解为什么像金黄色葡萄球菌这样的共生细菌会引起疾病，需要更详细地了解其自然状态下的宿主内进化。因此，我们详细研究了正常无症状携带的进化动态。我们使用 Illumina 平台对 13 个单一定植宿主的 131 个基因组进行了测序，研究了金黄色葡萄球菌短期进化过程中的多样性、选择、种群动态和传播。
我们描述了进化原材料产生的过程：微突变（点突变和小插入/缺失）、宏突变（大插入/缺失）以及移动元件（质粒和噬菌体）的丢失或获得。通过对同义突变、非同义突变和基因间突变的分析，我们发现了一个以纯化选择为主导的适应度景观，只有少数基因编码表面锚定蛋白和肠毒素的适应性变化。我们发现了宿主内种群大小随时间急剧波动的证据，这与定植和清除周期有关。我们使用一种新开发的群体遗传学方法来检测宿主之间的近期传播，发现了我们的一些研究对象之间存在近期传播的证据，包括一对携带耐甲氧西林金黄色葡萄球菌（MRSA）的夫妇。
这项研究开始描绘了一种重要的细菌病原体在其自然状态下无症状携带期间的宿主内进化情况。这些结果也具有更广泛的意义，因为它们为未来金黄色葡萄球菌侵袭性疾病进化的系统研究提供了基准。
