MODULATION OF OUTER MEMBRANE PROTEIN EXPRESSION IN HELICOBACTER PYLORI

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心赠款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 幽门螺杆菌通常感染胃，有时会导致消化性溃疡或胃癌。 H.幽门螺杆菌与胃上皮的附着是由一个大家族的外膜蛋白（OMP）介导的，其中研究得最好的是BabA。 感染了表达该基因的菌株的患者更有可能患上消化性溃疡或胃癌。 一个密切相关的蛋白质，BabB，显示出广泛的同源性与BabA，但其功能是未知的。 我们最近发现H.从实验感染的猕猴中回收的pylori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，由于相位变化，babA基因不表达。 缺乏BabA表达的菌株不粘附于在恒河猴胃上皮上表达的Leb血型抗原。 我们假设，在H。幽门螺杆菌OMP表达代表细菌表面的重塑，以避免宿主免疫或促进附着到胃上皮。 这些对BabA和BabB的研究将有助于正在进行的转化研究，这些研究旨在研究BabA和BabB作为候选疫苗的用途，并且还可能对基因组多样性在促进H.幽门。

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.