Helicobacter pylori acquisition of iron from the host

描述（由申请人提供）：幽门螺杆菌持续存在数十年，生活在胃内的各种微环境中。虽然大多数感染者无症状，但有些人因感染而发生溃疡或胃癌。H.已经发现幽门螺杆菌存在于细胞内和粘膜表面下的几个细胞层中，在这些细胞层中，从宿主分子中提取铁对于生长是必要的。铁代谢的研究，特别是H。幽门螺杆菌从宿主分子中捕获铁的能力由于缺乏合适的化学成分确定的培养基而受到阻碍。我们最近在培养方法上的进展使得在缺乏血清或螯合剂的限定培养基中研究铁代谢成为可能。我们证明了H.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的获得机制有很大不同。此外，我们表明，铁收购时，H。幽门螺杆菌与宿主上皮细胞共培养。我们试图详细探讨H.幽门螺杆菌对宿主铁源的利用（目的I）。宿主细胞增强H.将在Aim II中研究幽门螺杆菌铁获得。这些研究将极大地促进我们对H.幽门螺杆菌的铁获取机制和与宿主组织的相互作用，促进这种生物体的长期持久性。 公共卫生相关性：幽门螺杆菌导致溃疡和胃癌。为了引起严重的疾病，细菌必须能够从宿主那里窃取铁。探讨了H.幽门螺杆菌从人类获得铁的情况尚不清楚，本提案将对其进行研究。本研究的结果将有助于加深我们对H.幽门螺杆菌引起疾病，并可能导致新的治疗H。幽门感染

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.