Gene Expression during H. pylori-host interactions

幽门螺杆菌-宿主相互作用期间的基因表达

• 批准号: 7050834
• 负责人: JAY V. SOLNICK
• 金额: $ 3.86万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7050834
• 关键词: Helicobacter; Mexico; bacteria infection mechanism; bacterial genetics; bacterial proteins; bacterial toxins; biopsy; cellular immunity; clinical research; gastritis; gastrointestinal infection; genetic strain; genetic transcription; helper T lymphocyte; histopathology; host organism interaction; human subject; immune response; immunization; interleukin 8; nucleic acid repetitive sequence; patient oriented research; peptic ulcer; polymerase chain reaction; stomach neoplasms; tissue /cell culture; virulence

DESCRIPTION (provided by applicant): This research will be done primarily in Mexico City at the Institute Mexicano del Seguro Social in collaboration with Dr. Javier Torres as an extension of NIH grant # R01AI42081. Helicobacter pylori is an important human pathogen that causes peptic ulcer and gastric cancer, which is the second most common cause of cancer mortality worldwide and is especially common in Mexico and other developing countries. One of the most important questions in the pathobiology of H. pylori is why do some infected patients develop disease while others do not? Genomic diversity among bacterial strains partially explains the differences in clinical outcome. For example, disease occurs more commonly in patients infected with H. pylori strains that have the Gag pathogenicity island (PAI). We hypothesize that not only the presence of the PAI but also quantitative differences in expression of PAI and other virulence genes may be associated with the development of disease. We therefore propose to quantitate in vivo bacterial gene expression in H. pylori-infected patients with asymptomatic gastritis, and compare it to that in patients with peptic ulcer and gastric cancer. Gastric biopsies for culture and RNA extraction will be obtained from approximately 25 H. pylori- infected patients in each group. Expression of genes on the Cag PAI and selected other virulence genes will be measured directly from gastric biopsies using quantitative real-time RT-PCR. Acquisiton of patient samples, experimental procedures, and data analysis will be performed in the Torres lab with technical support from the Solnick lab, which is currently funded by NIAID to perform in vivo quantitative transcript profiling of H. pylori expression in experimentally infected rhesus macaques. The research proposed here is a direct extension of that work into H. pylori-infected humans with a well-characterized gastric histopathology. This will provide for the first time a quantitative profile of H. pylori gene expression in humans with different clinical outcomes, and may have implications for understanding the mechanisms by which H. pylori causes disease. Furthermore, the expertise acquired by the Torres lab can subsequently be applied more broadly to larger patient populations on a genome-wide scale, as well as to other infectious diseases that are important public health threats in Mexico and throughout Latin America.

描述（由申请人提供）：这项研究将主要在墨西哥城的 Mexicano del Seguro Social 研究所与 Javier Torres 博士合作进行，作为 NIH 拨款 # R01AI42081 的延伸。幽门螺杆菌是一种重要的人类病原体，可引起消化性溃疡和胃癌，是全球第二大癌症死亡原因，在墨西哥和其他发展中国家尤其常见。幽门螺杆菌病理学中最重要的问题之一是为什么一些感染患者会发病，而另一些患者则不会？细菌菌株之间的基因组多样性部分解释了临床结果的差异。例如，疾病更常见于感染具有 Gag 致病性岛 (PAI) 的幽门螺杆菌菌株的患者。我们推测，不仅 PAI 的存在，而且 PAI 和其他毒力基因表达的数量差异也可能与疾病的发生有关。因此，我们建议对幽门螺杆菌感染的无症状胃炎患者体内细菌基因表达进行定量，并将其与消化性溃疡和胃癌患者进行比较。将从每组中大约 25 名幽门螺杆菌感染患者中获得用于培养和 RNA 提取的胃活检。 Cag PAI 上的基因和选定的其他毒力基因的表达将使用定量实时 RT-PCR 直接从胃活检中测量。患者样本的采集、实验程序和数据分析将在 Torres 实验室中进行，并得到 Solnick 实验室的技术支持，该实验室目前由 NIAID 资助，对实验感染的恒河猴中的幽门螺杆菌表达进行体内定量转录分析。这里提出的研究是将这项工作直接延伸到具有明确胃组织病理学特征的幽门螺杆菌感染的人类中。这将首次提供具有不同临床结果的人类幽门螺杆菌基因表达的定量特征，并且可能对理解幽门螺杆菌引起疾病的机制具有影响。此外，托雷斯实验室获得的专业知识随后可以在全基因组范围内更广泛地应用于更大的患者群体，以及对墨西哥和整个拉丁美洲构成重要公共卫生威胁的其他传染病。