Oxidative Stress and Survival of Helicobacter pylori

描述(申请人提供)：幽门螺杆菌呈螺旋状 一种定植于人类胃粘膜的细菌，导致多种 炎症性胃病包括消化性溃疡、慢性胃炎、 胃下腺癌和淋巴瘤(粘膜相关淋巴瘤)。 炎症性疾病的严重程度与持续的 病原体的性质，慢性感染是主要的易感因素 致癌因素。这种持久性归因于病原体的严酷 适应人类胃的恶劣环境，这必须包括 避免酸性和对抗宿主防御机制。电池的电池 宿主产生的部分还原的氧物种和其他活性分子 破坏了细菌生存所需的细胞成分 病原体反过来又被成功产生的酶所抵消 病原体。目标是鉴定和表征抗氧化酶。 由幽门螺杆菌产生，用于对抗氧化应激和维持毒力(胃 殖民)。这将通过五个特定的靶向突变来实现 抗氧化基因。然后每个突变体都将被定性为它的能力 抵抗氧化应激，获得自发突变，生存 暴露在空气中，并定居在老鼠的胃里。与环境宿主相关的 信号(如铁、氧、粘蛋白、pH和氧化剂)可能 调控的五个基因中的每一个都会被确定，并有一些抗氧化剂 活动将被描述为特征。除了五种靶向抗氧化剂 活动，涉及蛋白质组学和DNA微阵列的全球方法将是 用于确定所表达的蛋白质的数量和性质 幽门螺杆菌对氧化应激条件的适应。

DESCRIPTION (provided by the applicant): Helicobacter pylori is a spiral bacterium that colonizes the gastric mucosa of humans, leading to a variety of inflammatory gastric diseases that include peptic ulcers, chronic gastritis, adenocarcinoma of the lower stomach, and MALToma (mucosal-associated lymphoma). The severity of the inflammatory-based disease is related to the persistent nature of the pathogen, and chronic infection is the predominant pre-disposing factor for carcinoma. The persistence is attributed to the pathogens' stringent adaptation to the harsh environment of the human stomach, which must include avoiding acidity and combating host defense mechanisms. The battery of host-produced partially reduced oxygen species and other reactive molecules that damage the bacterial cellular components needed for survival of the pathogen are in turn counteracted by enzymes produced by the successful pathogen. The goal is to identify and characterize the antioxidant enzymes produced by H pylori to combat oxidative stress and maintain virulence (stomach colonization). This will be approached by targeted mutagenesis of five specific antioxidant genes. Then each mutant will be characterized for its ability to withstand oxidative stresses, to acquire spontaneous mutations, to survive air-exposure, and to colonize mouse stomachs. The environmental host-related signals (such as iron, oxygen, mucin, pH, and oxidizing agent) that may regulate each of the five genes will be determined, and some of the antioxidant activities will be characterized. In addition to the five targeted antioxidant activities, global approaches involving proteomics and DNA microarray will be used to determine the number and nature of proteins that are expressed upon adaptation of H pylori to oxidative stress conditions.