Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
J Bacteriol. 2020 Dec 18;203(2). doi: 10.1128/JB.00495-20.
capsule polysaccharide is an important antiphagocytic virulence factor. The genes are regulated at the promoter element (P) upstream of the operon. P, which consists of a dominant SigB-dependent promoter and a weaker upstream SigA-dependent promoter, is activated by global regulator MgrA. How MgrA activates capsule is unclear. Here, we showed that MgrA directly bound to the P region and affected the SigA-dependent promoter. Interestingly, an electrophoretic mobility shift assay showed that MgrA bound to a large region of P, mainly downstream of the SigA-dependent promoter. We further showed that the ArlRS two-component system and the Agr quorum sensing system activated capsule primarily through MgrA in the early growth phases. The virulence of depends on the expression of various virulence factors, which is governed by a complex regulatory network. We have been using capsule as a model virulence factor to study virulence gene regulation in MgrA is one of the regulators of capsule and has a major effect on capsule production. However, how MgrA regulates capsule genes is not understood. In this study, we were able to define the mechanism involving MgrA regulation of capsule. In addition, we also delineated the role of MgrA in capsule regulatory pathways involving the key virulence regulators Agr and Arl. This study further advances our understanding of virulence gene regulation in , an important human pathogen.
荚膜多糖是一种重要的抗吞噬毒力因子。该基因在操纵子的启动子元件（P）上游受到调节。P 由一个占主导地位的 SigB 依赖性启动子和一个较弱的上游 SigA 依赖性启动子组成，由全局调节剂MgrA 激活。MgrA 如何激活荚膜尚不清楚。在这里，我们表明 MgrA 直接结合到 P 区域并影响 SigA 依赖性启动子。有趣的是，电泳迁移率变动分析表明，MgrA 结合到 P 的一个大区域，主要在 SigA 依赖性启动子的下游。我们进一步表明，ArlRS 双组分系统和 Agr 群体感应系统主要通过早期生长阶段的 MgrA 激活荚膜。取决于各种毒力因子的表达，依赖的毒力取决于各种毒力因子的表达，这受复杂的调控网络控制。我们一直使用荚膜作为模型毒力因子来研究毒力基因调控。MgrA 是荚膜的调节剂之一，对荚膜的产生有很大的影响。然而，MgrA 如何调节荚膜基因尚不清楚。在这项研究中，我们能够定义涉及 MgrA 调节荚膜的机制。此外，我们还描述了 MgrA 在涉及关键毒力调节剂 Agr 和 Arl 的荚膜调节途径中的作用。这项研究进一步提高了我们对重要人类病原体依赖的毒力基因调控的理解。
