Toward an understanding of the evolution of Staphylococcus aureus strain USA300 during colonization in community households.

Toward an understanding of the evolution of Staphylococcus aureus strain USA300 during colonization in community households.
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DOI:
10.1093/gbe/evs094
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发表时间:
2012
影响因子:
3.3
通讯作者:
Lowy FD
Lowy FD
中科院分区:
生物学2区
文献类型:
--
作者:
Uhlemann AC;Kennedy AD;Martens C;Porcella SF;Deleo FR;Lowy FD

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金黄色葡萄球菌是严重感染的常见原因,也是人类共生菌。社区相关的耐甲氧西林金黄色葡萄球菌的出现导致全球皮肤和软组织感染急剧增加。这种流行病是由有限数量的克隆推动的,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 15 个月内从三个不相关家庭纵向收集的 3 个临床和 5 个定植 USA300 分离株进行了比较全基因组测序。纳入其他地理上不同的 USA300 分离株的系统发育分析表明,除了一个之外,所有这些分离株都可能来自一个共同的近代祖先。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严重殖民化的家庭内。这种多样性允许更准确地跟踪人际 USA300 传输。对持续存在的 USA300 分离株的测序揭示了与金黄色葡萄球菌功能主要方面相关的基因突变: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的选定基因内多重多态性的积累,表明小基因组重排而不是从头单点突变。这种重排在金黄色葡萄球菌中并未得到充分重视,并且可能代表了菌株变异的新方法。微妙的基因变化可能有助于 USA300 的健康和持久性。对小基因组重排的阐明揭示了在环境生态位和病原体-宿主相互作用过程中金黄色葡萄球菌基因组定向多样化的潜在新的、有趣的机制。
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.
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发表时间: 2010-05-01
期刊: LANCET
影响因子: 168.9
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发表时间: 1998-12-01
期刊: MICROBIOLOGY-UK
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DOI: 10.1086/587907
发表时间: 2008-06-01
影响因子: 6.4
作者:
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