Role of the Accessory Gene Regulator agr in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis
Role of the Accessory Gene Regulator agr in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis
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DOI：
10.1128/iai.00046-11
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发表时间：
2011-05-01
影响因子：
3.1
通讯作者：
Otto, Michael
中科院分区：
文献类型：
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作者：
Cheung, Gordon Y. C.;Wang, Rong;Otto, Michael
社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）致病成功的分子基础尚不完全清楚，但差异基因表达已被认为至少部分解释了CA-MRSA菌株的高毒力。在这里，我们表明agr基因调控系统在最流行的CA-MRSA菌株USA 300的皮肤感染的发展中起着至关重要的作用。重要的是，我们的数据表明，这是由于CA-MRSA的agr调节子与医院相关的MRSA和实验室菌株之间的差异。特别是，在菌株USA 300中的agr调节导致毒素和外切酶的异常强的表达，纤维蛋白原结合蛋白的上调，结合纤维蛋白原的能力增加，以及甲氧西林抗性基因的表达增加。我们的研究结果表明，agr的功能是至关重要的CA-MRSA疾病，并表明，适应agr调节子有助于高致病性CA-MRSA的演变。
The molecular basis underlying the pathogenic success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is not completely understood, but differential gene expression has been suggested to account at least in part for the high virulence of CA-MRSA strains. Here, we show that the agr gene regulatory system has a crucial role in the development of skin infections in the most prevalent CA-MRSA strain USA300. Importantly, our data indicate that this is due to discrepancies between the agr regulon of CA-MRSA and those of hospital-associated MRSA and laboratory strains. In particular, agr regulation in strain USA300 led to exceptionally strong expression of toxins and exoenzymes, upregulation of fibrinogen-binding proteins, increased capacity to bind fibrinogen, and increased expression of methicillin resistance genes. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon contributed to the evolution of highly pathogenic CA-MRSA.