Laboratory of Human Bacterial Pathogenesis, NIAID, NIH, Bldg. 33, 1W10, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Infect Immun. 2011 May;79(5):1927-35. doi: 10.1128/IAI.00046-11. Epub 2011 Mar 14.
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.
社区获得性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，但已有人提出差异基因表达至少部分解释了 CA-MRSA 菌株的高毒力。在这里，我们表明agr 基因调控系统在最常见的 CA-MRSA 菌株 USA300 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 和医院相关 MRSA 以及实验室菌株之间的 agr 调控子存在差异。具体而言，USA300 菌株中的 agr 调控导致毒素和外切酶的表达异常强烈，纤维蛋白原结合蛋白的上调，对纤维蛋白原的结合能力增强，以及耐甲氧西林基因的表达增强。我们的研究结果表明，agr 功能对于 CA-MRSA 疾病至关重要，并表明 agr 调控子的适应性有助于高度致病性 CA-MRSA 的进化。
