MODULATION OF OUTER MEMBRANE PROTEIN EXPRESSION IN HELICOBACTER PYLORI

幽门螺杆菌外膜蛋白表达的调节

• 批准号: 8357315
• 负责人: JAY V. SOLNICK
• 金额: $ 7.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357315
• 关键词: Blood Group Antigens; California; Chronic; Epithelium; Family; Funding; Genes; Genome; Grant; Helicobacter pylori; Immunity; Infection; Macaca; Macaca mulatta; Mediating; Membrane Proteins; Modification; National Center for Research Resources; Patients; Peptic Ulcer; Phase; Primates; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Role; Source; Stomach; Surface; Translational Research; United States National Institutes of Health; Variant; cost; malignant stomach neoplasm; protein expression; vaccine candidate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Helicobacter pylori commonly infects the stomach, where it sometimes causes peptic ulcer disease or gastric cancer. H. pylori attachment to the gastric epithelium is mediated by a large family of outer membrane proteins (OMPs), the best studied of which is BabA. Patients infected with strains that express it are more likely to develop peptic ulcer or gastric cancer. A closely related protein, BabB, shows extensive homology with BabA, but its function is unknown. We recently showed that H. pylori strains recovered from experimentally infected macaques had lost expression of BabA. In some cases the babA gene was replaced by babB and in other cases the babA gene was not expressed due to phase variation. Strains lacking BabA expression did not adhere to the Leb blood group antigen that is expressed on rhesus gastric epithelium. We hypothesize that modifications in H. pylori OMP expression represent a remodeling of the bacterial surface so as to avoid host immunity or promote attachment to the gastric epithelium. These studies of BabA and BabB will contribute to ongoing translational research that seek to investigate the use of BabA and BabB as vaccine candidates, and also may have broad implications for the role of genome diversity in promoting chronic infection with H. pylori.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 幽门螺杆菌通常会感染胃，有时会导致消化性溃疡病或胃癌。 幽门螺杆菌附着在胃上皮的附着是由大型外膜蛋白（OMP）介导的，其中最好的研究是Baba。 感染了表达菌株的患者更有可能患上消化性溃疡或胃癌。 密切相关的蛋白质BABB与BABA表现出广泛的同源性，但其功能尚不清楚。 我们最近表明，从实验感染的猕猴中回收的幽门螺杆菌菌株失去了BABA的表达。 在某些情况下，BABA基因被BABB取代，在其他情况下，BABA基因并未由于相变而表达。 缺乏BABA表达的菌株并未遵守在恒河猴上皮上表达的LEB血液组抗原。 我们假设幽门螺杆菌中的修饰表达表示细菌表面的重塑，以避免宿主免疫或促进胃皮细胞的附着。 这些对BABA和BABB的研究将有助于持续的转化研究，这些研究旨在研究BABA和BABB作为候选疫苗的使用，并且可能对基因组多样性在促进幽门螺杆菌慢性感染中的作用具有广泛的影响。