Contribution of Helicobacter pylori HomA and HomB to colonization and disease

摘要： 幽门螺杆菌慢性感染了世界50%的人口，是导致胃病的重要原因 癌症。在胃里，细菌与宿主细胞相互作用，并阐述直接 影响疾病病因学。为了保持在这一生态位内的定植，幽门螺杆菌需要机制来 耐受上皮细胞和粘液脱落过程中的机械清除，以及 防止免疫系统检测和清除的机制。编码外膜蛋白的基因 膜蛋白(Omps)约占幽门螺杆菌基因组的4%，这很可能是 广泛的一系列蛋白质可能在建立和维持感染中发挥关键作用 黏附和/或免疫逃避。因此，OMP很可能是宿主细菌的关键成分 界面。此外，几种可变的OMP已被证明与更严重的疾病有关 胃溃疡和胃癌等表现。包括在这些与毒力相关的OMP中 是幽门螺杆菌外膜蛋白B(Homb)。Homb与Homa高度相似，两人一直 被证明有能力占据幽门螺杆菌基因组中的两个主要位点，即A位和B位； 菌株同时携带两种基因，而有些菌株携带其中一种基因。目前还没有研究表明 两个可能的基因组位置对Homa和Homb的影响。此外，尽管事实是 体外研究表明Homb在黏附中起作用，但实际上还没有其他分子研究 评估Homa和Homb在幽门螺杆菌感染过程中的作用。为了更好地了解 对于这两个OMP的表达和功能，我们提出了详细的分子研究，将直接 检测HOMA和HOMB在模拟发现的环境压力下的表达 在胃环境中。此外，利用构建的一系列等基因突变体和 携带所有可能的HOMA和HOMB单基因组合的互补菌株，我们将 直接评估HOMA和HOMB在蒙古沙土鼠的定植和疾病发展中的作用 感染模式。所描述的研究将提供有关表达和功能的新信息 霍马和霍姆。这些信息可能反过来为新疗法的发展提供线索 专门针对这些OMP设计的。

Abstract: Helicobacter pylori chronically infects 50% of the world’s population and is a significant cause of gastric cancer. In the stomach, the bacterium interacts with host cells and elaborates virulence factors that directly influence disease etiology. To maintain colonization within this niche, H. pylori needs mechanisms to withstand mechanical clearance during the sloughing of epithelial cells and mucous, as well as mechanisms to prevent detection and clearance by the immune system. Genes encoding for outer membrane proteins (OMPs) constitute approximately 4% of the H. pylori genome, and it is likely that this extensive array of proteins may play a crucial role in establishing and maintaining infection by aiding in adhesion and/or immune evasion. Thus, the OMPs likely serve as key elements of the host-bacterium interface. In addition, several variable OMPs have been shown to be associated with more severe disease presentations such as gastric ulcers and gastric cancer. Included among these virulence-associated OMPs is Helicobacter Outer Membrane Protein B (HomB). HomB is highly similar to HomA and the two have been shown to have the ability to occupy two primary loci, locus A and locus B in the H. pylori genome; some strains carry both genes, while some carry one or the other. There are no studies that address the implications of the two possible genomic locations for homA and homB. Furthermore, despite the fact that in vitro studies indicate a role for HomB in adherence, virtually no other molecular studies have been conducted to assess the role of HomA and HomB during H. pylori infection. To gain a better understanding of the expression and function of these two OMPs, we propose detailed molecular studies that will directly examine expression of homA and homB in response to environmental stresses that mimic those found within the gastric environment. Furthermore, using a series of constructed isogenic mutant and complementation strains that carry all possible single gene combinations of homA and homB, we will directly assess the role of HomA and HomB in colonization and disease progression in the Mongolian gerbil model of infection. The described studies will provide novel information concerning expression and function of HomA and HomB. This information may in turn provide clues to the development of novel therapeutics that are designed to specifically target these OMPs.