Queck Shu Y, Jameson-Lee Max, Villaruz Amer E, Bach Thanh-Huy L, Khan Burhan A, Sturdevant Daniel E, Ricklefs Stacey M, Li Min, Otto Michael
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Mol Cell. 2008 Oct 10;32(1):150-8. doi: 10.1016/j.molcel.2008.08.005.
Cell-density-dependent gene regulation by quorum-sensing systems has a crucial function in bacterial physiology and pathogenesis. We demonstrate here that the Staphylococcus aureus agr quorum-sensing regulon is divided into (1) control of metabolism and PSM cytolysin genes, which occurs independently of the small regulatory RNA RNAIII, and (2) RNAIII-dependent control of additional virulence genes. Remarkably, PSM expression was regulated by direct binding of the AgrA response regulator. Our findings suggest that quorum-sensing regulation of PSMs was established before wide-ranging control of virulence was added to the agr regulon, which likely occurred by development of the RNAIII-encoding region around the gene encoding the PSM delta-toxin. Moreover, the agr regulon in the community-associated methicillin-resistant S. aureus MW2 considerably differed from that previously determined using laboratory strains. By establishing a two-level model of quorum-sensing target gene regulation in S. aureus, our study gives important insight into the evolution of virulence control in this leading human pathogen.
群体感应系统对细胞密度依赖性基因的调控在细菌生理学和发病机制中具有关键作用。我们在此证明，金黄色葡萄球菌的agr群体感应调控子分为两部分：（1）对代谢和PSM溶细胞素基因的控制，这一过程独立于小调节RNA RNAIII发生；（2）对其他毒力基因的RNAIII依赖性控制。值得注意的是，PSM的表达是由AgrA反应调节因子的直接结合来调控的。我们的研究结果表明，PSM的群体感应调控在agr调控子广泛控制毒力之前就已确立，这可能是由于围绕PSM δ-毒素编码基因的RNAIII编码区域的进化所致。此外，社区相关耐甲氧西林金黄色葡萄球菌MW2中的agr调控子与先前使用实验室菌株确定的调控子有很大差异。通过建立金黄色葡萄球菌群体感应靶基因调控的两级模型，我们的研究为这种主要人类病原体中毒力控制的进化提供了重要见解。
