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. 2018 Aug 24;200(18). doi: 10.1128/JB.00203-18. Print 2018 Sep 15.
Capsule is one of many virulence factors produced by , and its expression is highly regulated. Here, we report the repression of capsule by direct interaction of XdrA and CodY with the capsule promoter region. We found, by footprinting analyses, that XdrA repressed capsule by binding to a broad region that extended from upstream of the -35 region of the promoter to the coding region of , the first gene of the 16-gene operon. Footprinting analyses also revealed that CodY bound to a large region that overlapped extensively with that of XdrA. We found that repression of the genes in the mutant could be achieved by the overexpression of but not vice versa, suggesting is epistatic to However, we found XdrA had no effect on CodY expression. These results suggest that XdrA plays a secondary role in capsule regulation by promoting CodY repression of the genes. Oxacillin slightly induced expression and reduced promoter activity, but the effect of oxacillin on capsule was not mediated through XdrA. employs a complex regulatory network to coordinate the expression of various virulence genes to achieve successful infections. How virulence genes are coordinately regulated is still poorly understood. We have been studying capsule regulation as a model system to explore regulatory networking in In this study, we found that XdrA and CodY have broad binding sites that overlap extensively in the capsule promoter region. Our results also suggest that XdrA assists CodY in the repression of capsule. As capsule gene regulation by DNA-binding regulators has not been fully investigated, the results presented here fill an important knowledge gap, thereby further advancing our understanding of the global virulence regulatory network in .
荚膜是 产生的众多毒力因子之一，其表达受到高度调控。在这里，我们报告了 XdrA 和 CodY 通过与荚膜启动子区域直接相互作用来抑制荚膜的表达。通过足迹分析，我们发现 XdrA 通过结合从启动子的-35 区域上游延伸到 16 基因 操纵子的第一个基因 的广泛区域来抑制荚膜。足迹分析还表明 CodY 结合到与 XdrA 广泛重叠的大片段区域。我们发现，在 突变体中，通过过表达 可以实现 基因的抑制，但反之则不行，这表明 对 是上位的。然而，我们发现 XdrA 对 CodY 的表达没有影响。这些结果表明，XdrA 通过促进 CodY 对 基因的抑制，在荚膜调节中发挥次要作用。苯唑西林轻微诱导 表达并降低 启动子活性，但苯唑西林对荚膜的影响不是通过 XdrA 介导的。 采用复杂的调控网络来协调各种毒力基因的表达，以实现成功感染。毒力基因如何协调调控仍知之甚少。我们一直在研究荚膜调节作为一个模型系统，以探索 中调节网络。在这项研究中，我们发现 XdrA 和 CodY 在荚膜启动子区域具有广泛重叠的结合位点。我们的结果还表明，XdrA 有助于 CodY 抑制荚膜。由于 DNA 结合调节剂对荚膜基因调节的研究尚未完全开展，因此这里提出的结果填补了一个重要的知识空白，从而进一步加深了我们对 中全局毒力调控网络的理解。
