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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification
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Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification

机译：流行性社区相关耐甲氧西林金黄色葡萄球菌：最近的克隆扩展和多样化。

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Emerging and re-emerging infectious diseases, especially those caused by drug-resistant bacteria, are a major problem worldwide. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) appeared rapidly and unexpectedly in the United States, resulting in an epidemic caused primarily by isolates classified as USA300. The evolutionary and molecular underpinnings of this epidemic are poorly understood. Specifically, it is unclear whether there has been clonal emergence of USA300 isolates or evolutionary convergence toward a hypervirulent phenotype resulting in the independent appearance of similar organisms. To definitively resolve this issue and understand the phylogeny of USA300 isolates, we used comparative whole-genome sequencing to analyze 10 USA300 patient isolates from eight states in diverse geographic regions of the United States and multiple types of human infection. Eight of 10 isolates analyzed had very few single nucleotide polymorphisms (SNPs) and thus were closely related, indicating recent diversification rather than convergence. Unexpectedly, 2 of the clonal isolates had significantly reduced mortality in a mouse sepsis model compared with the reference isolate (P = 0.0002), providing strong support to the idea that minimal genetic change in the bacterial genome can have profound effects on virulence. Taken together, our results demonstrate that there has been recent clonal expansion and diversification of a subset of isolates classified as USA300. The findings add an evolutionary dimension to the epidemiology and emergence of USA300 and suggest a similar mechanism for the pandemic occurrence and spread of penicillin-resistant S. aureus (known as phage-type 80/81 S. aureus) in the 1950s.
机译：新兴和重新出现的传染病，尤其是由耐药菌引起的传染病，是世界范围内的主要问题。在美国，与社区相关的耐甲氧西林的金黄色葡萄球菌（CA-MRSA）迅速出现，出乎意料，导致流行病主要由分类为USA300的分离株引起。对这种流行病的进化和分子基础了解甚少。具体而言，尚不清楚是否存在USA300分离株的克隆出现或向高毒力表型的进化趋同导致相似生物体的独立出现。为了最终解决此问题并了解USA300分离株的系统发生，我们使用了比较全基因组测序方法，分析了来自美国不同地理区域和多种人类感染类型的八个州的10个USA300患者分离株。分析的10个分离株中有8个几乎没有单核苷酸多态性（SNP），因此密切相关，表明最近是多样化而不是趋同。出乎意料的是，与参考分离株相比，其中2个克隆分离株在小鼠脓毒症模型中的死亡率显着降低（P = 0.0002），为细菌基因组中最小的遗传变化可对毒力产生深远影响的观点提供了有力的支持。综上所述，我们的结果表明，分类为USA300的分离株的子集近来已得到了克隆扩展和多样化。这些发现为USA300的流行病学和出现增加了进化的维度，并为1950年代耐青霉素的金黄色葡萄球菌（称为噬菌体型80/81金黄色葡萄球菌）的大流行发生和传播提供了类似的机制。

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