DNA EXCHANGE DURING STOMACH COLONIZATION BY HELICOBACTER PYLORI

幽门螺杆菌在胃定植期间的 DNA 交换

• 批准号: 8021032
• 负责人: Marion Shonn Dorer
• 金额: $ 1.4万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-10 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8021032
• 关键词: Antibiotic Resistance; Applications Grants; Area; Bacteria; Cancer Etiology; Carcinogens; Cessation of life; Chronic; Clinical; Competence; DNA; Disease; Environment; Faculty; Future; Gastric Adenocarcinoma; Gastritis; Goals; Helicobacter Infections; Helicobacter pylori; Human; Infection; Inflammatory Response; Laboratories; Lead; Mentors; Mission; Modality; National Institute of Diabetes and Digestive and Kidney Diseases; Pathway interactions; Peptic Ulcer; Pharmaceutical Preparations; Population; Positioning Attribute; Preparation; Public Health; Publications; Research; Risk; Scientist; Stomach; Stress; Therapeutic; Time; Ulcer; Work; Writing; fighting; genetic analysis; malignant stomach neoplasm; mouse model; mucosa-associated lymphoid tissue lymphoma; prevent; research study; resistance allele; skills; treatment strategy

DESCRIPTION (provided by applicant): Helicobacter pylori is the only bacterium that is a class I carcinogen [1]. I study H. pylori, [sic] because of its enormous impact on public health: at least 50% of the world population is persistently infected with this carcinogen. H. pylori-related disease [sic] includes chronic active gastritis, peptic ulcer disease, MALT lymphoma and gastric adenocarcinoma, the second leading cause of cancer-related deaths in the world. Understanding the mechanisms that H. pylori uses for stomach colonization will lead to new treatment strategies to prevent these diseases. We have found that H. pylori require natural competence, the ability to take up environmental DNA, for stomach colonization. It has been hypothesized that natural competence helps this bacterium adapt to changes in host environment over long periods of time; however our experiments show that natural competence is important at early times during stomach colonization, suggesting it has a second function. This proposal has two Aims: to determine 1) when and 2) how H. pylori natural competence is required during stomach colonization in a mouse model. Completion of these Aims will hone my skills in genetic analysis of H. pylori and manipulation of the mouse model, thus preparing me to begin my own laboratory as an independent scientist. I will work with a mentoring committee to develop three areas: this research to its full potential, my speaking skills in preparation for a search for a faculty position, and my writing skills for future publications and grant applications. In my own laboratory, the long-term goal will be to study mechanisms of natural competence important for stomach colonization and this work will lead to treatment modalities. Targeting the natural competence machinery is an intriguing therapeutic strategy, because it will: i) inhibit colonization, thereby increasing clearance of the bacterium ii) prevent the bacterium from exchanging antibiotic resistance alleles. These studies fulfill the mission of the NIDDK by identifying mechanism for fighting H. pylori infection, the major cause of chronic active gastritis, peptic ulcer disease, MALT lymphoma and gastric adenocarcinoma. Peptic Ulcers are not caused by stress, but rather infection with a bacterium called Helicobacter pylori, which also causes gastric cancer. Studying the bacterium will help us develop new drugs that will rid people of the infection and reduced greatly their risk of developing ulcers or stomach cancer.

描述（由申请人提供）： 幽门螺杆菌是唯一是I类致癌的细菌[1]。我研究H. Pylori，因为它对公共卫生的巨大影响：至少有50％的世界人口持续感染了这种致癌物。幽门螺杆菌相关疾病[SIC]包括慢性活性胃炎，消化性溃疡疾病，麦芽淋巴瘤和胃腺癌，这是世界上与癌症相关死亡的第二大主要原因。了解幽门螺杆菌用于胃定植的机制将导致预防这些疾病的新治疗策略。我们发现，幽门螺杆菌需要自然能力，具有环境DNA的能力，以进行胃定植。已经假设自然能力有助于这种细菌在长时间内适应宿主环境的变化。但是，我们的实验表明，自然能力在胃定植期间的早期很重要，这表明它具有第二个功能。该提议有两个目的：确定1）何时和2）在小鼠模型中胃定植期间如何需要幽门螺杆菌自然能力。这些目标的完成将磨练我在幽门螺杆菌的遗传分析和小鼠模型的操纵方面的技能，从而使我准备开始自己作为独立科学家的实验室。我将与一个指导委员会合作开发三个领域：这项研究具有全部潜力，我的口语技巧，准备寻找教师职位，以及我为未来出版物和赠款申请的写作技巧。在我自己的实验室中，长期目标是研究对胃定植至关重要的自然能力机制，这项工作将导致治疗方式。靶向自然能力机械是一种有趣的治疗策略，因为它将：i）抑制定殖，从而增加细菌的清除率II）防止细菌交换抗生素耐药性等位基因。这些研究通过鉴定与幽门螺杆菌感染的机制（慢性活性胃炎，消化性溃疡，麦芽淋巴瘤和胃腺癌的主要原因）来履行NIDDK的任务。消化性溃疡不是由压力引起的，而是用称为幽门螺杆菌的细菌感染，这也会引起胃癌。研究细菌将有助于我们开发新药，这些药物将消除感染者，并大大降低患溃疡或胃癌的风险。