Helicobacter pylori acquisition of iron from the host

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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.