Oxidative Stress and Survival of Helicobacter pylori

描述（由申请人提供）：幽门螺杆菌是一种螺旋型 一种寄生在人类胃粘膜上的细菌，导致多种 炎性胃病包括消化性溃疡，慢性胃炎， 胃下部腺癌和MALT瘤（粘膜相关淋巴瘤）。 基于炎症的疾病的严重程度与持续的 病原体的性质，慢性感染是主要的诱发因素 癌的因素。这种持久性归因于病原体的严格 适应人类胃的恶劣环境，其中必须包括 避免酸性和对抗宿主防御机制。的电池 宿主产生的部分还原的氧物质和其它活性分子 破坏了细菌生存所需的细胞成分， 病原体反过来又被成功的微生物产生的酶所抵消。 病原体我们的目标是识别和表征抗氧化酶 由幽门螺杆菌产生，以对抗氧化应激并保持毒力（胃 殖民化）。这将通过五种特异性的靶向诱变来实现。 抗氧化基因然后每个突变体将被描述其能力， 承受氧化压力，获得自发突变，生存 暴露在空气中，并在小鼠胃中定植。环境宿主相关 信号（如铁、氧、粘蛋白、pH和氧化剂）， 调节每五个基因将被确定，和一些抗氧化剂 活动将有特点。除了五种针对性的抗氧化剂 活动，涉及蛋白质组学和DNA微阵列的全球方法将被 用于确定表达于细胞表面的蛋白质的数量和性质。 幽门螺杆菌适应氧化应激条件。

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.