Department of Microbiology, New York University School of Medicine, New York, New York, USA.
J Bacteriol. 2012 Aug;194(16):4355-65. doi: 10.1128/JB.00706-12. Epub 2012 Jun 8.
Staphylococcus aureus is a significant human pathogen that is capable of infecting a wide range of host tissues. This bacterium is able to evade the host immune response by utilizing a repertoire of virulence factors. These factors are tightly regulated by various two-component systems (TCS) and transcription factors. Previous studies have suggested that transcriptional regulation of a subset of immunomodulators, known as the staphylococcal superantigen-like proteins (Ssls), is mediated by the master regulators accessory gene regulator (Agr) TCS, S. aureus exoprotein expression (Sae) TCS, and Rot. Here we demonstrate that Rot and SaeR, the response regulator of the Sae TCS, synergize to coordinate the activation of the ssl promoters. We have determined that both transcription factors are required, but that neither is sufficient, for promoter activation. This regulatory scheme is mediated by direct binding of both transcription factors to the ssl promoters. We also demonstrate that clinically relevant methicillin-resistant S. aureus (MRSA) strains respond to neutrophils via the Sae TCS to upregulate the expression of ssls. Until now, Rot and the Sae TCS have been proposed to work in opposition of one another on their target genes. This is the first example of these two regulators working in concert to activate promoters.
金黄色葡萄球菌是一种重要的人类病原体，能够感染宿主的多种组织。该细菌能够通过利用一系列毒力因子来逃避宿主的免疫反应。这些因子受到各种双组分系统（TCS）和转录因子的严格调节。先前的研究表明，一组免疫调节剂（称为葡萄球菌超抗原样蛋白（Ssls））的转录调控由主调控辅助基因调节（Agr）TCS、金黄色葡萄球菌外蛋白表达（Sae）TCS 和 Rot 介导。在这里，我们证明 Rot 和 SaeR（Sae TCS 的反应调节剂）协同作用以协调 ssl 启动子的激活。我们已经确定这两种转录因子都需要，但都不足以激活启动子。这种调节方案是通过这两种转录因子直接结合 ssl 启动子介导的。我们还证明，临床上相关的耐甲氧西林金黄色葡萄球菌（MRSA）菌株通过 Sae TCS 对中性粒细胞作出反应，上调 ssls 的表达。到目前为止，Rot 和 Sae TCS 被提议在其靶基因上相互拮抗。这是这两个调节剂协同作用以激活启动子的第一个例子。
