CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae.
CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae.
复制标题
CpsR 是一种 GntR 家族调节因子，可转录调节荚膜多糖生物合成并控制肺炎链球菌的细菌毒力。
DOI：
10.1038/srep29255
复制
发表时间：
2016-07-08
影响因子：
4.6
通讯作者：
Yin Y
中科院分区：
文献类型：
--
作者：
Wu K;Xu H;Zheng Y;Wang L;Zhang X;Yin Y
荚膜表达的转录调控对于肺炎球菌从携带到感染的转变至关重要，但其潜在机制仍不完全清楚。在这里，我们描述了由GntR家族调节因子CpsR调节的荚膜多糖，这是最重要的肺炎球菌毒力因子之一。电泳迁移率变动分析表明，CpsR和cps启动子（cpsp）之间的直接相互作用，它们的相互作用可以竞争性干扰葡萄糖。DNA酶I足迹分析将结合位点定位于相对于S中cps基因座转录起始位点的-146至-114碱基对区域。pneumoniae D39.我们发现CpsR负性控制cps基因座的转录，从而控制CPS的产生，这通过在ΔcpsR互补菌株中微调CpsR的表达得到证实。CpsR在补充菌株中的表达增加导致对全血介导的杀伤的抗性降低，表明CpsR-cpsp相互作用在建立侵袭性感染中的保护作用。最后，动物实验表明，CpsR-cpsp相互作用是必要的肺炎球菌定植和侵袭性感染。综上所述，我们的研究结果提供了一个深入的了解调节胶囊生产介导的CpsR及其在肺炎球菌发病机制中的重要作用。
Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region −146 to −114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a ΔcpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis.