Transcriptional Regulation in Helicobacter pylori during Infection

描述（由申请人提供）：幽门螺杆菌（H.幽门螺杆菌（pylori）是一种感染大约三分之一的美国人口和一半的世界人口的胃的细菌，并且可能是最常见的人类细菌感染。为了实现这一点，H。幽门螺杆菌通过复杂的机制克服胃的非常低的pH环境。了解H. pylori对低pH的适应将具有重大的科学和医学意义。为此，我们将研究调节pH和胃细胞接触相关基因表达的蛋白质在H。幽门。我们专注于两个新的序列特异性DNA结合蛋白。HP0222及其同源物HP0564，我们根据我们的结构和生化研究确定了它们的功能。HP0222在中性条件下适度转录，但在H. pylori在酸性pH下培养或与胃细胞接触。我们假设HP 0222和HP 0564是在H. pylori毒力我们希望找到这些蛋白质所识别的DNA序列，并确定它们对H. pylori基因。我们将追求三个具体目标：1。由HP 0222和HP 0564识别的共有DNA序列，2. HP 0222和HP 0564与DNA结合的结构，3. HP 0222和HP 0564在发病机制中的作用。完成的目标将确定一组基因和一个新的调节机制，在H。pylori发病机制受HP0222和HP0564调控的基因将是未来基因破坏实验的候选基因。 幽门螺杆菌是一种细菌，感染了大约三分之一的美国人口和一半的世界人口的胃，是最常见的人类细菌感染。它与十二指肠溃疡、胃炎、胃溃疡、胃癌和胃淋巴瘤等常见和严重的胃肠道疾病有因果关系。这项研究的结果将有助于设计新的和具体的治疗方法，以消除H。幽门螺杆菌，而不诉诸强大的副作用诱导抗生素，目标普遍共享的生化途径。

DESCRIPTION (provided by applicant): Helicobacter pylori (H. pylori) is a bacterium that infects the stomachs of around one third of the US population and half of the world population, and is probably the most common human bacterial infection. To accomplish this, H. pylori overcomes the very low pH environment of the stomach via complex mechanisms. Understanding H. pylori adaptation to low pH will have great scientific and medical significance. Towards this end, we will study proteins that regulate pH and gastric cell contact-associated gene expression in H. pylori. We focus on two novel sequence-specific DNA binding proteins. HP0222 and its homolog HP0564, whose functions we established based on our structural and biochemical studies. HP0222 is moderately transcribed under neutral conditions, but becomes up regulated in H. pylori cultured at acidic pH or in contact with gastric cells. We hypothesize that HP0222 and HP0564 are transcriptional regulators that play a role in H. pylori virulence. We propose to find the DNA sequences recognized by these proteins and to determine their effects on the transcription of H. pylori genes. We will pursue three specific aims: 1. consensus DNA sequences recognized by HP0222 and HP0564, 2. structures of HP0222 and HP0564 bound to DNA, 3. HP0222 and HP0564 role in pathogenesis. Completed aims will identify a set of genes and a novel regulatory mechanism important in H. pylori pathogenesis. Genes regulated by HP0222 and HP0564 will be candidates for future gene disruption experiments. Helicobacter pylori is a bacterium that infects the stomachs of around one third of the US population and half of the world population, and is the most common human bacterial infection. It is causatively linked with both common and severe gastrointestinal diseases like duodenal ulcer, gastritis, gastric ulcer, gastric carcinoma and gastric lymphoma. Results of this research will help design novel and specific treatments to eradicate H. pylori without resorting to potent side effect- inducing antibiotics that target universally shared biochemical pathways.