Laboratory of Molecular Microbiology, Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
J Bacteriol. 2012 Jul;194(13):3327-35. doi: 10.1128/JB.00199-12. Epub 2012 Apr 20.
The capacity of pathogens to respond to environmental signals, such as iron concentration, is key to bacterial survival and establishment of a successful infection. Bacillus cereus is a widely distributed bacterium with distinct pathogenic properties. Hemolysin II (HlyII) is one of its pore-forming cytotoxins and has been shown to be involved in bacterial pathogenicity in a number of cell and animal models. Unlike many other B. cereus pathogenicity factors, HlyII is not regulated by pleiotropic transcriptional regulator PlcR but is controlled by its own regulator, HlyIIR. Using a combination of in vivo and in vitro techniques, we show that hlyII expression is also negatively regulated by iron by the global regulator Fur via direct interaction with the hlyII promoter. DNase I footprinting and in vitro transcription experiments indicate that Fur prevents RNA polymerase binding to the hlyII promoter. HlyII expression profiles demonstrate that both HlyIIR and Fur regulate HlyII expression in a concerted fashion, with the effect of Fur being maximal in the early stages of bacterial growth. In sum, these results show that Fur serves as a transcriptional repressor for hlyII expression.
病原体对环境信号（如铁浓度）作出反应的能力是细菌存活和成功感染的关键。蜡样芽胞杆菌是一种分布广泛的细菌，具有独特的致病性。溶血素 II（HlyII）是其一种形成孔的细胞毒素，已被证明在许多细胞和动物模型中参与细菌的致病性。与许多其他蜡样芽胞杆菌致病因子不同，HlyII 不受多效转录调节剂 PlcR 调控，而是由其自身的调节剂 HlyIIR 控制。我们使用体内和体外技术的组合表明，hlyII 的表达也受到铁的负调控，这是通过全局调节剂 Fur 通过与 hlyII 启动子的直接相互作用实现的。DNase I 足迹和体外转录实验表明，Fur 阻止 RNA 聚合酶与 hlyII 启动子结合。HlyII 表达谱表明，HlyIIR 和 Fur 以协同方式调节 HlyII 的表达，Fur 的作用在细菌生长的早期阶段最大。总之，这些结果表明 Fur 作为 hlyII 表达的转录抑制剂。
