Division of Infectious Diseases, Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY, USA.
Genome Biol Evol. 2012;4(12):1275-85. doi: 10.1093/gbe/evs094.
Staphylococcus aureus is a frequent cause of serious infections and also a human commensal. The emergence of community-associated methicillin-resistant S. aureus led to a dramatic increase in skin and soft tissue infections worldwide. This epidemic has been driven by a limited number of clones, such as USA300 in the United States. To better understand the extent of USA300 evolution and diversification within communities, we performed comparative whole-genome sequencing of three clinical and five colonizing USA300 isolates collected longitudinally from three unrelated households over a 15-month period. Phylogenetic analysis that incorporated additional geographically diverse USA300 isolates indicated that all but one likely arose from a common recent ancestor. Although limited genetic adaptation occurred over the study period, the greatest genetic heterogeneity occurred between isolates from different households and within one heavily colonized household. This diversity allowed for a more accurate tracking of interpersonal USA300 transmission. Sequencing of persisting USA300 isolates revealed mutations in genes involved in major aspects of S. aureus function: adhesion, cell wall biosynthesis, virulence, and carbohydrate metabolism. Genetic variations also included accumulation of multiple polymorphisms within select genes of two multigene operons, suggestive of small genome rearrangements rather than de novo single point mutations. Such rearrangements have been underappreciated in S. aureus and may represent novel means of strain variation. Subtle genetic changes may contribute to USA300 fitness and persistence. Elucidation of small genome rearrangements reveals a potentially new and intriguing mechanism of directed S. aureus genome diversification in environmental niches and during pathogen-host interactions.
金黄色葡萄球菌是一种常见的严重感染病原体，也是人体共生菌。社区相关耐甲氧西林金黄色葡萄球菌的出现导致了全球范围内皮肤和软组织感染的急剧增加。这种流行是由少数几个克隆引起的，例如美国的 USA300。为了更好地了解 USA300 在社区内的进化和多样化程度，我们对从三个无关家庭中在 15 个月内收集的三个临床和五个定植 USA300 分离株进行了比较全基因组测序。包含更多地理上多样化的 USA300 分离株的系统发育分析表明，除了一个之外，所有分离株可能都来自一个共同的近期祖先。尽管在研究期间发生了有限的遗传适应，但最大的遗传异质性发生在来自不同家庭的分离株之间以及一个高度定植的家庭内。这种多样性允许更准确地追踪人际 USA300 传播。对持续存在的 USA300 分离株的测序揭示了参与金黄色葡萄球菌功能主要方面的基因中的突变：粘附、细胞壁生物合成、毒力和碳水化合物代谢。遗传变异还包括两个多基因操纵子中多个选择基因内的多个多态性，提示小基因组重排而不是从头单个点突变。在金黄色葡萄球菌中，这种重排被低估了，可能代表了菌株变异的新手段。遗传变异包括两个多基因操纵子中多个选择基因内的多个多态性，提示小基因组重排而不是从头单个点突变。在金黄色葡萄球菌中，这种重排被低估了，可能代表了菌株变异的新手段。遗传变异包括两个多基因操纵子中多个选择基因内的多个多态性，提示小基因组重排而不是从头单个点突变。在金黄色葡萄球菌中，这种重排被低估了，可能代表了菌株变异的新手段。
