Helicobacter pylori acquisition of iron from the host

描述(申请人提供)：幽门螺杆菌持续存在几十年，生活在胃内的各种微环境中。虽然大多数感染者没有症状，但也有一些人会因感染而患上溃疡或胃癌。幽门螺杆菌已被发现在细胞内和粘膜表面下的几个细胞层中，从宿主分子中提取铁是生长所必需的。对铁代谢的研究，特别是幽门螺杆菌从宿主分子中捕获铁的能力的研究，由于缺乏合适的化学定义的介质而受到阻碍。我们在培养方法上的最新进展现在使得在缺乏血清或螯合剂的特定介质中研究铁代谢成为可能。我们发现，幽门螺杆菌可以从几种宿主铁结合蛋白中获得铁，包括血红蛋白、乳铁蛋白和转铁蛋白；然而，它的获得机制似乎与其他病原体有很大不同。此外，我们还表明，当幽门螺杆菌与宿主上皮细胞共培养时，铁的获取被增强。我们试图详细地探索幽门螺杆菌利用宿主铁源的效率和动态(目标I)。宿主细胞促进幽门螺杆菌铁获取的机制将在AIM II中进行研究。这些研究将极大地促进我们对幽门螺杆菌铁获取机制的理解，以及与宿主组织的相互作用，从而促进这种生物的长期存留。 公共卫生相关性：幽门螺杆菌可导致溃疡和胃癌。为了引起严重的疾病，细菌必须能够从它们的宿主那里窃取铁。幽门螺杆菌从人体获取铁的机制尚不清楚，将在本提案中进行研究。这项研究的结果将提高我们对幽门螺杆菌致病机制的理解，并可能导致治疗幽门螺杆菌感染的新方法。

DESCRIPTION (provided by applicant): Helicobacter pylori persist for decades, living in various microenvironments within the stomach. Although most infected individuals are asymptomatic, some individuals develop ulcers or gastric cancer as a result of infection. H. pylori has been found intracellularly and several cell layers beneath the mucosal surface where extraction of iron from host molecules would be necessary for growth. Studies of iron metabolism, and particularly the ability of H. pylori to capture iron from host molecules, have been hampered by lack of a suitable chemically defined media. Our recent advances in culture methods now make it possible to study iron metabolism in a defined medium lacking serum or chelators. We show that H. pylori can obtain iron from several host iron-binding proteins, including hemoglobin, lactoferrin, and transferrin; however, its acquisition mechanisms appear to differ substantially from those of other pathogens. Furthermore, we show that iron acquisition is enhanced when H. pylori is co-cultured with host epithelial cells. We seek to explore in detail the efficiency and dynamics of H. pylori utilization of host iron sources (Aim I). The mechanism by which host cells enhance H. pylori iron acquisition will be investigated in Aim II. These studies will greatly advance our understanding of H. pylori's iron acquisition mechanisms and the interactions with host tissue that promotes long-term persistence by this organism. PUBLIC HEALTH RELEVANCE: Helicobacter pylori causes ulcers and gastric cancer. In order to cause serious disease, bacteria must be able to steal iron from their host. The mechanisms by which H. pylori acquire iron from humans are not clearly known and will be studied in this proposal. The results of this study will improve our understanding of how H. pylori causes disease and could lead to new treatments for H. pylori infections.