Serum Proteins Influencing Helicobacter pylori Growth

描述（由申请人提供）：幽门螺杆菌继续折磨全世界大部分人口，引起从胃炎和溃疡到癌症的疾病。这种微生物在没有血清的情况下仍然难以培养，并且对有益于H的血清成分知之甚少。幽门生长我们的初步数据表明，铜蓝蛋白（cp）从人或牛血清和至少一个其他身份不明的血清蛋白是负责增强生长。我们推测CP和另一种蛋白协同作用为H提供铁。幽门螺杆菌或保护细菌免受氧化应激。这项建议的具体目标是： 1.证实铜蓝蛋白是一种增强H.幽门生长 2.探讨铜蓝蛋白对H.幽门生长 3.确定增加H所需的其他血清蛋白。幽门生长 各种生化试验和克隆来源的铜蓝蛋白同系物将用于实现目标1。目标2将涉及铁的吸收和抗氧化应激的存在下， 血浆铜蓝蛋白。我们将通过使用先进的质谱分析来鉴定血清组分中存在或不存在的蛋白质，然后对纯化的蛋白质进行测试，从而实现目标3。 本研究的结果可能对H.幽门螺杆菌和其他苛养细菌。虽然许多研究已经解决了粘附因子的重要定植，很少有人知道其他宿主因子所需的H。幽门螺杆菌的生长和发病机制。此外，许多其他致病物种仍然难以或不可能在体外培养。更全面地了解血清蛋白与细菌的相互作用也可能导致其他生物体培养的进步。

DESCRIPTION (provided by applicant): Helicobacter pylori continues to afflict a large percentage of the human population worldwide, causing diseases ranging from gastritis and ulcers to cancer. This organism remains difficult to cultivate without serum, and little is known about serum components beneficial for H. pylori growth. Our preliminary data indicate that ceruloplasmin (cp) from human or bovine serum and at least one other unidentified serum protein are responsible for augmenting growth. We hypothesize that cp and another protein synergize to supply iron to H. pylori or protect the bacterium from oxidative stress. The specific aims of this proposal are to: 1. Confirm the identity of ceruloplasmin as one of the serum proteins augmenting H. pylori growth. 2. Determine the mechanism of ceruloplasmin effect on H. pylori growth. 3. Identify the other serum protein(s) required for augmentation of H. pylori growth. Various biochemical tests and cloned sources of ceruloplasmin homologs will be used to achieve aim 1. Aim 2 will involve examination of iron uptake and resistance to oxidative stress in the presence of ceruloplasmin. We will accomplish aim 3 by using advanced mass spectroscopic analysis to identify proteins present in or absent from serum fractions, followed by testing of purified proteins. Results from this study may have wide-ranging impacts on the study of H. pylori and other fastidious bacteria. Although many studies have addressed adhesion factors important for colonization, little is known about other host factors required for H. pylori growth and pathogenesis. Furthermore, numerous other pathogenic species remain difficult or impossible to cultivate in vitro. A more complete understanding of serum proteins interacting with bacteria could lead to advancements in cultivation of other organisms as well.